HRASGTPase HRas

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "12740440"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "14500341"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "22821884"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "40934300"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "9020151"
        }
      ],
      "value": "Signal transducer in the Ras-MAPK signaling pathway that regulates cell proliferation and survival (PubMed:22821884). Ras proteins bind GDP/GTP and possess intrinsic GTPase activity (PubMed:12740440, PubMed:14500341, PubMed:9020151). 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": "9020151"
      }
    ]
  }
}

{
  "texts": [
    {
      "value": "Alternates between an inactive form bound to GDP and an active form bound to GTP. Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by a GTPase-activating protein (GAP)"
    }
  ],
  "commentType": "ACTIVITY REGULATION"
}

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

{
  "names": {
    "recommendedName": {
      "fullName": {
        "value": "GTPase HRas"
      },
      "ecNumbers": [
        {
          "evidences": [
            {
              "evidenceCode": "ECO:0000269",
              "source": "PubMed",
              "id": "9020151"
            }
          ],
          "value": "3.6.5.2"
        }
      ]
    },
    "alternativeNames": [
      {
        "fullName": {
          "value": "H-Ras-1"
        }
      },
      {
        "fullName": {
          "value": "Ha-Ras"
        }
      },
      {
        "fullName": {
          "value": "Transforming protein p21"
        }
      },
      {
        "fullName": {
          "value": "c-H-ras"
        }
      },
      {
        "fullName": {
          "value": "p21ras"
        }
      }
    ],
    "contains": [
      {
        "recommendedName": {
          "fullName": {
            "value": "GTPase HRas, N-terminally processed"
          }
        }
      }
    ],
    "flag": "Precursor"
  },
  "genes": [
    {
      "geneName": {
        "value": "HRAS"
      },
      "synonyms": [
        {
          "value": "HRAS1"
        }
      ]
    }
  ]
}

{
  "commentType": "DISEASE",
  "disease": {
    "diseaseId": "Costello syndrome",
    "diseaseAccession": "DI-01437",
    "acronym": "CSTLO",
    "description": "A rare condition characterized by prenatally increased growth, postnatal growth deficiency, intellectual disability, distinctive facial appearance, cardiovascular abnormalities (typically pulmonic stenosis, hypertrophic cardiomyopathy and/or atrial tachycardia), tumor predisposition, skin and musculoskeletal abnormalities.",
    "diseaseCrossReference": {
      "database": "MIM",
      "id": "218040"
    },
    "evidences": [
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "16170316"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "16329078"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "16443854"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "17054105"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "18039947"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "18247425"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "19995790"
      }
    ]
  },
  "note": {
    "texts": [
      {
        "value": "The disease is caused by variants affecting the gene represented in this entry"
      }
    ]
  }
}

{
  "commentType": "DISEASE",
  "disease": {
    "diseaseId": "Congenital myopathy with excess of muscle spindles",
    "diseaseAccession": "DI-01411",
    "acronym": "CMEMS",
    "description": "Variant of Costello syndrome.",
    "diseaseCrossReference": {
      "database": "MIM",
      "id": "218040"
    },
    "evidences": [
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "17412879"
      }
    ]
  },
  "note": {
    "texts": [
      {
        "value": "The disease is caused by variants affecting the gene represented in this entry"
      }
    ]
  }
}

{
  "commentType": "DISEASE",
  "disease": {
    "diseaseId": "Thyroid cancer, non-medullary, 2",
    "diseaseAccession": "DI-04532",
    "acronym": "NMTC2",
    "description": "A form of non-medullary thyroid cancer (NMTC), a cancer characterized by tumors originating from the thyroid follicular cells. NMTCs represent approximately 95% of all cases of thyroid cancer and are classified into papillary, follicular, Hurthle cell, and anaplastic neoplasms.",
    "diseaseCrossReference": {
      "database": "MIM",
      "id": "188470"
    },
    "evidences": [
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "12727991"
      }
    ]
  },
  "note": {
    "texts": [
      {
        "value": "Disease susceptibility is associated with variants affecting the gene represented in this entry"
      }
    ]
  }
}

{
  "commentType": "DISEASE",
  "note": {
    "texts": [
      {
        "evidences": [
          {
            "evidenceCode": "ECO:0000269",
            "source": "PubMed",
            "id": "3670300"
          }
        ],
        "value": "Mutations which change positions 12, 13 or 61 activate the potential of HRAS to transform cultured cells and are implicated in a variety of human tumors"
      }
    ]
  }
}

{
  "commentType": "DISEASE",
  "disease": {
    "diseaseId": "Bladder cancer",
    "diseaseAccession": "DI-02612",
    "acronym": "BLC",
    "description": "A malignancy originating in tissues of the urinary bladder. It often presents with multiple tumors appearing at different times and at different sites in the bladder. Most bladder cancers are transitional cell carcinomas that begin in cells that normally make up the inner lining of the bladder. Other types of bladder cancer include squamous cell carcinoma (cancer that begins in thin, flat cells) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids). Bladder cancer is a complex disorder with both genetic and environmental influences.",
    "diseaseCrossReference": {
      "database": "MIM",
      "id": "109800"
    },
    "evidences": [
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "6298635"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "6844927"
      }
    ]
  },
  "note": {
    "texts": [
      {
        "value": "Disease susceptibility is associated with 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": "22683711"
      }
    ]
  },
  "note": {
    "texts": [
      {
        "value": "The disease is caused by variants affecting the gene represented in this entry"
      }
    ]
  }
}

{
  "texts": [
    {
      "value": "Palmitoylated by the ZDHHC9-GOLGA7 complex. A continuous cycle of de- and re-palmitoylation regulates rapid exchange between plasma membrane and Golgi"
    }
  ],
  "commentType": "PTM"
}

{
  "texts": [
    {
      "value": "S-nitrosylated; critical for redox regulation. Important for stimulating guanine nucleotide exchange. No structural perturbation on nitrosylation"
    }
  ],
  "commentType": "PTM"
}

{
  "texts": [
    {
      "value": "The covalent modification of cysteine by 15-deoxy-Delta12,14-prostaglandin-J2 is autocatalytic and reversible. It may occur as an alternative to other cysteine modifications, such as S-nitrosylation and S-palmitoylation"
    }
  ],
  "commentType": "PTM"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000250"
        }
      ],
      "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": "Fatty-acylated at Lys-170"
    }
  ],
  "commentType": "PTM"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "30442762"
        }
      ],
      "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"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "8626575"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "8626586"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "9632667"
        }
      ],
      "value": "(Microbial infection) Glucosylated at Thr-35 by P.sordellii toxin TcsL (PubMed:19744486, PubMed:8626575, PubMed:8626586, PubMed:9632667). Monoglucosylation completely prevents the recognition of the downstream effector, blocking the GTPases in their inactive form, leading to inhibit Ras signaling (PubMed:8626575, PubMed:8626586, PubMed:9632667)"
    }
  ],
  "commentType": "PTM"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "14500341"
        }
      ],
      "value": "Widely expressed"
    }
  ],
  "commentType": "TISSUE SPECIFICITY"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000250",
          "source": "UniProtKB",
          "id": "P20171"
        },
        {
          "evidenceCode": "ECO:0000250",
          "source": "UniProtKB",
          "id": "Q61411"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "10369681"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "10608844"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "11022048"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "11257115"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "11598133"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "11980706"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "14500341"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "17230191"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "18596699"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "35522713"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "35768504"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "35831509"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "36175670"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "40934300"
        }
      ],
      "value": "In its GTP-bound form interacts with PLCE1 (PubMed:11022048). Interacts with TBC1D10C (PubMed:17230191). Interacts with RGL3 (By similarity). Interacts with HSPD1 (By similarity). Found in a complex with at least BRAF, HRAS, MAP2K1, MAPK3 and RGS14 (By similarity). Interacts (active GTP-bound form) with RGS14 (via RBD 1 domain) (By similarity). Forms a signaling complex with RASGRP1 and DGKZ (PubMed:11257115). Interacts with RASSF5 (PubMed:18596699). Interacts with PDE6D (PubMed:11980706). Interacts with IKZF3 (PubMed:10369681). Interacts with RACK1 (PubMed:14500341). Interacts with PIK3CG; the interaction is required for membrane recruitment and beta-gamma G protein dimer-dependent activation of the PI3K gamma complex PIK3CG:PIK3R6 (By similarity). Interacts with RAPGEF2 (PubMed:10608844, PubMed:11598133). 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:35768504, PubMed:35831509, PubMed:36175670). Interacts (GTP-bound form) with MAPKAP1/SIN1; inhibiting H-Ras/HRAS activity (PubMed:35522713). Interacts (GDP-bound form) with LZTR1; this interaction mediates HRAS ubiquitination by BCR E3 ligase complex (PubMed:40934300)"
    }
  ],
  "commentType": "SUBUNIT"
}