MGP Database

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MGP001785

UniProt Annotations

Entry Information
Gene NameKirsten rat sarcoma viral oncogene homolog
Protein EntryRASK_HUMAN
UniProt IDP01116
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Comment=Isoforms differ in the C-terminal region which is encoded by two alternative exons (IVA and IVB).; Name=2A; Synonyms=K-Ras4A; IsoId=P01116-1; Sequence=Displayed; Name=2B; Synonyms=K-Ras4B; IsoId=P01116-2, P01118-1; Sequence=VSP_011140, VSP_011141; Note=Variant in position: 152:V->G (in NS3). Variant in position: 153:D->V (in CFC2 and NS3, exhibits only minor alterations in its in vitro biochemical behavior compared to wild-type protein). Variant in position: 156:F->I (in NS3/CFC2). Variant in position: 156:F->L (found in a patient with Costello syndrome, exhibits an increase in intrinsic and guanine nucleotide exchange factor catalyzed nucleotide exchange in combination with an impaired GTPase-activating protein-stimulated GTP hydrolysis but functional in interaction with effectors).;
DiseaseCardiofaciocutaneous syndrome 2 (CFC2) [MIM:615278]: A form of cardiofaciocutaneous syndrome, a multiple congenital anomaly disorder characterized by a distinctive facial appearance, heart defects and mental retardation. 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. {ECO:0000269|PubMed:16474404, ECO:0000269|PubMed:16474405, ECO:0000269|PubMed:17056636, ECO:0000269|PubMed:21797849}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseGastric cancer (GASC) [MIM:613659]: 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. {ECO:0000269|PubMed:14534542, ECO:0000269|PubMed:3034404, ECO:0000269|PubMed:7773929}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseLeukemia, acute myelogenous (AML) [MIM:601626]: 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. {ECO:0000269|PubMed:8955068}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseLeukemia, juvenile myelomonocytic (JMML) [MIM:607785]: 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. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseNoonan syndrome 3 (NS3) [MIM:609942]: 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. {ECO:0000269|PubMed:16474405, ECO:0000269|PubMed:16773572, ECO:0000269|PubMed:17056636, ECO:0000269|PubMed:17468812, ECO:0000269|PubMed:19396835}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseNote=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.
DiseaseNote=KRAS mutations are involved in cancer development.
Enzyme RegulationAlternates 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). Interaction with SOS1 promotes exchange of bound GDP by GTP. {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:22566140, ECO:0000269|PubMed:22711838}.
FunctionRas proteins bind GDP/GTP and possess intrinsic GTPase activity. Plays an important role in the regulation of cell proliferation (PubMed:23698361, PubMed:22711838). {ECO:0000269|PubMed:22711838, ECO:0000269|PubMed:23698361, ECO:0000305}.
InteractionQ04631:Fnta (xeno); NbExp=2; IntAct=EBI-367427, EBI-602447; P04049:RAF1; NbExp=2; IntAct=EBI-367427, EBI-365996; P50749:RASSF2; NbExp=2; IntAct=EBI-367415, EBI-960081;
PtmAcetylation at Lys-104 prevents interaction with guanine nucleotide exchange factors (GEFs). {ECO:0000269|PubMed:22711838, ECO:0000269|Ref.17}.
SimilarityBelongs to the small GTPase superfamily. Ras family. {ECO:0000305}.
Subcellular LocationCell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361}; Lipid-anchor {ECO:0000305|PubMed:23698361}; Cytoplasmic side {ECO:0000305|PubMed:23698361}. Cytoplasm, cytosol {ECO:0000269|PubMed:23698361}.
SubunitInteracts with PHLPP. 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). {ECO:0000250|UniProtKB:P08644, ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361}.
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/KRASID91.html";
Web ResourceName=SHMPD; Note=The Singapore human mutation and polymorphism database; URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=KRAS";
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