KRASGTPase KRas

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000250",
          "source": "UniProtKB",
          "id": "P08644"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "20949621"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "22711838"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "23698361"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "24623306"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "39809765"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "40934300"
        }
      ],
      "value": "Signal transducer in the Ras-MAPK signaling pathway that regulates cell proliferation and survival (PubMed:22711838, PubMed:23698361). Ras proteins bind GDP/GTP and possess intrinsic GTPase activity (PubMed:20949621, PubMed:39809765). Activates MAPK1/MAPK3 resulting in phosphorylation and ultimately degradation of GJA1 (By similarity). Plays a role in promoting oncogenic events by inducing transcriptional silencing of tumor suppressor genes (TSGs) in colorectal cancer (CRC) cells in a ZNF304-dependent manner (PubMed:24623306). Recognized by LZTR1 that mediates its ubiquitination by a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex (PubMed:40934300)"
    }
  ],
  "commentType": "FUNCTION"
}

{
  "commentType": "CATALYTIC ACTIVITY",
  "reaction": {
    "name": "GTP + H2O = GDP + phosphate + H(+)",
    "reactionCrossReferences": [
      {
        "database": "Rhea",
        "id": "RHEA:19669"
      },
      {
        "database": "ChEBI",
        "id": "CHEBI:15377"
      },
      {
        "database": "ChEBI",
        "id": "CHEBI:15378"
      },
      {
        "database": "ChEBI",
        "id": "CHEBI:37565"
      },
      {
        "database": "ChEBI",
        "id": "CHEBI:43474"
      },
      {
        "database": "ChEBI",
        "id": "CHEBI:58189"
      }
    ],
    "ecNumber": "3.6.5.2",
    "evidences": [
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "20949621"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "39809765"
      }
    ]
  }
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "22431598"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "22566140"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "22711838"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "39809765"
        }
      ],
      "value": "Alternates between an inactive form bound to GDP and an active form bound to GTP (PubMed:22566140, PubMed:22431598, PubMed:39809765). Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by a GTPase-activating protein (GAP) (PubMed:22711838). Interaction with SOS1 promotes exchange of bound GDP to GTP (PubMed:22566140, PubMed:22431598, PubMed:39809765)"
    }
  ],
  "commentType": "ACTIVITY REGULATION"
}

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

{
  "names": {
    "recommendedName": {
      "fullName": {
        "value": "GTPase KRas"
      },
      "ecNumbers": [
        {
          "evidences": [
            {
              "evidenceCode": "ECO:0000269",
              "source": "PubMed",
              "id": "20949621"
            },
            {
              "evidenceCode": "ECO:0000269",
              "source": "PubMed",
              "id": "39809765"
            }
          ],
          "value": "3.6.5.2"
        }
      ]
    },
    "alternativeNames": [
      {
        "fullName": {
          "value": "K-Ras 2"
        }
      },
      {
        "fullName": {
          "value": "Ki-Ras"
        }
      },
      {
        "fullName": {
          "value": "c-K-ras"
        }
      },
      {
        "fullName": {
          "value": "c-Ki-ras"
        }
      }
    ],
    "contains": [
      {
        "recommendedName": {
          "fullName": {
            "value": "GTPase KRas, N-terminally processed"
          }
        }
      }
    ],
    "flag": "Precursor"
  },
  "genes": [
    {
      "geneName": {
        "value": "KRAS"
      },
      "synonyms": [
        {
          "value": "KRAS2"
        },
        {
          "value": "RASK2"
        }
      ]
    }
  ]
}

{
  "commentType": "DISEASE",
  "disease": {
    "diseaseId": "Leukemia, acute myelogenous",
    "diseaseAccession": "DI-01171",
    "acronym": "AML",
    "description": "A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes.",
    "diseaseCrossReference": {
      "database": "MIM",
      "id": "601626"
    },
    "evidences": [
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "8955068"
      }
    ]
  },
  "note": {
    "texts": [
      {
        "value": "The disease is caused by variants affecting the gene represented in this entry"
      }
    ]
  }
}

{
  "commentType": "DISEASE",
  "disease": {
    "diseaseId": "Leukemia, juvenile myelomonocytic",
    "diseaseAccession": "DI-01851",
    "acronym": "JMML",
    "description": "An aggressive pediatric myelodysplastic syndrome/myeloproliferative disorder characterized by malignant transformation in the hematopoietic stem cell compartment with proliferation of differentiated progeny. Patients have splenomegaly, enlarged lymph nodes, rashes, and hemorrhages.",
    "diseaseCrossReference": {
      "database": "MIM",
      "id": "607785"
    },
    "evidences": [
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "17332249"
      }
    ]
  },
  "note": {
    "texts": [
      {
        "value": "The disease is caused by variants affecting the gene represented in this entry"
      }
    ]
  }
}

{
  "commentType": "DISEASE",
  "disease": {
    "diseaseId": "Noonan syndrome 3",
    "diseaseAccession": "DI-02073",
    "acronym": "NS3",
    "description": "A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells.",
    "diseaseCrossReference": {
      "database": "MIM",
      "id": "609942"
    },
    "evidences": [
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "16474405"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "16773572"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "17056636"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "17468812"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "19396835"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "20949621"
      }
    ]
  },
  "note": {
    "texts": [
      {
        "value": "The disease is caused by variants affecting the gene represented in this entry"
      }
    ]
  }
}

{
  "commentType": "DISEASE",
  "disease": {
    "diseaseId": "Gastric cancer",
    "diseaseAccession": "DI-02971",
    "acronym": "GASC",
    "description": "A malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease.",
    "diseaseCrossReference": {
      "database": "MIM",
      "id": "613659"
    },
    "evidences": [
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "14534542"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "3034404"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "7773929"
      }
    ]
  },
  "note": {
    "texts": [
      {
        "value": "The disease is caused by variants affecting the gene represented in this entry"
      }
    ]
  }
}

{
  "commentType": "DISEASE",
  "note": {
    "texts": [
      {
        "evidences": [
          {
            "evidenceCode": "ECO:0000269",
            "source": "PubMed",
            "id": "16247081"
          }
        ],
        "value": "Defects in KRAS are a cause of pylocytic astrocytoma (PA). Pylocytic astrocytomas are neoplasms of the brain and spinal cord derived from glial cells which vary from histologically benign forms to highly anaplastic and malignant tumors"
      }
    ]
  }
}

{
  "commentType": "DISEASE",
  "disease": {
    "diseaseId": "Cardiofaciocutaneous syndrome 2",
    "diseaseAccession": "DI-03779",
    "acronym": "CFC2",
    "description": "A form of cardiofaciocutaneous syndrome, a multiple congenital anomaly disorder characterized by a distinctive facial appearance, heart defects and intellectual disability. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. CFC2 patients often do not have the skin abnormalities, such as ichthyosis, hyperkeratosis, and hemangioma observed in CFC1.",
    "diseaseCrossReference": {
      "database": "MIM",
      "id": "615278"
    },
    "evidences": [
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "16474404"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "16474405"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "17056636"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "20949621"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "21797849"
      }
    ]
  },
  "note": {
    "texts": [
      {
        "value": "The disease is caused by variants affecting the gene represented in this entry"
      }
    ]
  }
}

{
  "commentType": "DISEASE",
  "note": {
    "texts": [
      {
        "evidences": [
          {
            "evidenceCode": "ECO:0000269",
            "source": "PubMed",
            "id": "14534542"
          },
          {
            "evidenceCode": "ECO:0000269",
            "source": "PubMed",
            "id": "1553789"
          },
          {
            "evidenceCode": "ECO:0000269",
            "source": "PubMed",
            "id": "16533793"
          },
          {
            "evidenceCode": "ECO:0000269",
            "source": "PubMed",
            "id": "24623306"
          },
          {
            "evidenceCode": "ECO:0000269",
            "source": "PubMed",
            "id": "3034404"
          },
          {
            "evidenceCode": "ECO:0000269",
            "source": "PubMed",
            "id": "3627975"
          },
          {
            "evidenceCode": "ECO:0000269",
            "source": "PubMed",
            "id": "6092920"
          },
          {
            "evidenceCode": "ECO:0000269",
            "source": "PubMed",
            "id": "6695174"
          },
          {
            "evidenceCode": "ECO:0000269",
            "source": "PubMed",
            "id": "7773929"
          }
        ],
        "value": "KRAS mutations are involved in cancer development"
      }
    ]
  }
}

{
  "commentType": "DISEASE",
  "disease": {
    "diseaseId": "Oculoectodermal syndrome",
    "diseaseAccession": "DI-05645",
    "acronym": "OES",
    "description": "A syndrome characterized by the association of epibulbar dermoids and aplasia cutis congenita. Affected individuals show multiple, asymmetric, atrophic, non-scarring and hairless regions that may be associated with hamartomas. Ectodermal changes include linear hyperpigmentation that may follow the lines of Blaschko and rarely epidermal nevus-like lesions. Epibulbar dermoids may be uni-or bilateral. Additional ocular anomalies such as skin tags of the upper eyelid, rarely optic nerve or retinal changes, and microphthalmia can be present. The phenotypic expression is highly variable, and various other abnormalities have occasionally been reported including growth failure, lymphedema, cardiovascular defects, as well as neurodevelopmental symptoms like developmental delay, epilepsy, learning difficulties, and behavioral abnormalities. Benign tumor-like lesions such as nonossifying fibromas of the long bones and giant cell granulomas of the jaws have repeatedly been observed and appear to be age-dependent, becoming a common manifestation in individuals aged 5 years or older.",
    "diseaseCrossReference": {
      "database": "MIM",
      "id": "600268"
    },
    "evidences": [
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "25808193"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "26970110"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "30891959"
      }
    ]
  },
  "note": {
    "texts": [
      {
        "value": "The disease is caused by variants affecting the gene represented in this entry"
      }
    ]
  }
}

{
  "commentType": "DISEASE",
  "disease": {
    "diseaseId": "Schimmelpenning-Feuerstein-Mims syndrome",
    "diseaseAccession": "DI-03512",
    "acronym": "SFM",
    "description": "A disease characterized by sebaceous nevi, often on the face, associated with variable ipsilateral abnormalities of the central nervous system, ocular anomalies, and skeletal defects. Many oral manifestations have been reported, not only including hypoplastic and malformed teeth, and mucosal papillomatosis, but also ankyloglossia, hemihyperplastic tongue, intraoral nevus, giant cell granuloma, ameloblastoma, bone cysts, follicular cysts, oligodontia, and odontodysplasia. Sebaceous nevi follow the lines of Blaschko and these can continue as linear intraoral lesions, as in mucosal papillomatosis.",
    "diseaseCrossReference": {
      "database": "MIM",
      "id": "163200"
    },
    "evidences": [
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "30891959"
      }
    ]
  },
  "note": {
    "texts": [
      {
        "value": "The disease is caused by variants affecting the gene represented in this entry"
      }
    ]
  }
}

{
  "commentType": "DISEASE",
  "disease": {
    "diseaseId": "RAS-associated autoimmune leukoproliferative disorder 2",
    "diseaseAccession": "DI-07162",
    "acronym": "RALD2",
    "description": "A disease characterized by lymphadenopathy, splenomegaly, and autoimmunity causing hemolytic anemia, idiopathic thrombocytopenic purpura, and neutropenia.",
    "diseaseCrossReference": {
      "database": "MIM",
      "id": "621582"
    },
    "evidences": [
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "21063026"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "21079152"
      }
    ]
  },
  "note": {
    "texts": [
      {
        "value": "The disease is caused by variants affecting the gene represented in this entry"
      }
    ]
  }
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "22711838"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "Reference",
          "id": "Ref.17"
        }
      ],
      "value": "Acetylation at Lys-104 prevents interaction with guanine nucleotide exchange factors (GEFs)"
    }
  ],
  "commentType": "PTM"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "29239724"
        }
      ],
      "value": "Palmitoylated at Lys-182, Lys-184 and Lys-185 (PubMed:29239724). Palmitoylation on lysine residues is promoted by palmitoylation at Cys-180 (PubMed:29239724). Lysine-depalmitoylation by SIRT2 promotes its localization to endomembranes in endocytic pathways (PubMed:29239724)"
    }
  ],
  "commentType": "PTM"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000305",
          "source": "PubMed",
          "id": "30442762"
        },
        {
          "evidenceCode": "ECO:0000305",
          "source": "PubMed",
          "id": "30442766"
        }
      ],
      "value": "Ubiquitinated by the BCR(LZTR1) E3 ubiquitin ligase complex at Lys-170 in a non-degradative manner, leading to inhibit Ras signaling by decreasing Ras association with membranes"
    }
  ],
  "commentType": "PTM"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "19744486"
        }
      ],
      "value": "(Microbial infection) Glucosylated at Thr-35 by P.sordellii toxin TcsL"
    }
  ],
  "commentType": "PTM"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "23524970"
        }
      ],
      "value": "Expressed throughout the epidermis, but weakly expressed in the stratum corneum and dermis (at protein level)"
    }
  ],
  "commentType": "TISSUE SPECIFICITY"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000250",
          "source": "UniProtKB",
          "id": "P08644"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "20709748"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "22431598"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "23524970"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "23698361"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "24415755"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "28619714"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "34380736"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "35522713"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "35768504"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "35830882"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "35831509"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "36175670"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "40934300"
        }
      ],
      "value": "Interacts with PHLPP (By similarity). Interacts (active GTP-bound form preferentially) with RGS14 (By similarity). Interacts (when farnesylated) with PDE6D; this promotes dissociation from the cell membrane (PubMed:23698361). Interacts with SOS1 (PubMed:22431598). Interacts (when farnesylated) with GPR31 (PubMed:28619714). Interacts with RAP1GDS1 (PubMed:20709748, PubMed:24415755). Interacts (active GTP-bound form) with both SHOC2 and PP1c (all isoforms) to form a tertiary complex; SHOC2 and PP1c preferably bind M-Ras/MRAS, but they also bind K-Ras/KRAS, N-Ras/NRAS and H-Ras/HRAS (PubMed:23524970, PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670). Interacts (GTP-bound form) with MAPKAP1/SIN1; inhibiting K-Ras/KRAS activity (PubMed:34380736, PubMed:35522713). Interacts (GDP-bound form) with LZTR1; this interaction mediates KRAS ubiquitination by BCR E3 ligase complex (PubMed:40934300)"
    }
  ],
  "commentType": "SUBUNIT"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "28619714"
        }
      ],
      "value": "Interacts with GPR31; in a farnelysation-dependent manner"
    }
  ],
  "commentType": "SUBUNIT",
  "molecule": "Isoform 2B"
}