K-Ras

K-Ras acts as a molecular on/off switch. Once it is turned on it recruits and activates proteins necessary for the propagation of growth factor and other receptors' signal, such as c-Raf and PI 3-kinase. KRAS binds to GTP in the active state and possesses an intrinsic enzymatic activity which cleaves the terminal phosphate of the nucleotide converting it to GDP. Upon conversion of GTP to GDP, KRAS is turned off. The rate of conversion is usually slow but can be sped up dramatically by an accessory protein of the GTPase activating protein (GAP) class, for example RasGAP. In turn KRAS can bind to proteins of the Guanine Nucleotide Exchange Factor (GEF) class, for example SOS1, which forces the release of bound nucleotide. Subsequently, KRAS binds GTP present in the cytosol and the GEF is released from ras-GTP. Other members of the Ras family include: HRAS and NRAS. These proteins all are regulated in the same manner and appear to differ largely in their sites of action within the cell.

K-Ras Related Areas

 

K-Ras Related Pathways

• EGFR Signaling Pathway
• TGF-beta Signaling
• VEGF Signaling
• Cytokine Receptor Signaling

K-Ras Alternative Names

K-Ras, KRAS, C-K-RAS, K-RAS2A, K-RAS2B, K-RAS4A, K-RAS4B, KI-RAS, KRAS1, KRAS2, NS, NS3, RASK2 [Homo sapiens]
K-Ras, Kras, RP24-359O2.1, AI929937, Ki-ras, Kras-2, Kras2, MGC7141, p21B, ras [Mus musculus]

Summaries for K-Ras

Entrez Gene summary for K-Ras :

KRAS acts as a molecular on/off switch. Once it is turned on it recruits and activates proteins necessary for the propagation of growth factor and other receptors' signal, such as c-Raf and PI 3-kinase. KRAS binds to GTP in the active state and possesses an intrinsic enzymatic activity which cleaves the terminal phosphate of the nucleotide converting it to GDP. Upon conversion of GTP to GDP, KRAS is turned off. The rate of conversion is usually slow but can be sped up dramatically by an accessory protein of the GTPase activating protein (GAP) class, for example RasGAP. In turn KRAS can bind to proteins of the Guanine Nucleotide Exchange Factor (GEF) class, for example SOS1, which forces the release of bound nucleotide. Subsequently, KRAS binds GTP present in the cytosol and the GEF is released from ras-GTP. Other members of the Ras family include: HRAS and NRAS. These proteins all are regulated in the same manner and appear to differ largely in their sites of action within

OMIM - description for K-Ras :

The KRAS gene encodes the human cellular homolog of a transforming gene isolated from the Kirsten rat sarcoma virus. The RAS proteins are GDP/GTP-binding proteins that act as intracellular signal transducers. The most well-studied members of the RAS (derived from 'RAt Sarcoma' virus) gene family include KRAS, HRAS (190020), and NRAS (164790). These genes encode immunologically related proteins with a molecular mass of 21 kD and are homologs of rodent sarcoma virus genes that have transforming abilities. While these wildtype cellular proteins in humans play a vital role in normal tissue signaling, including proliferation, differentiation, and senescence, mutated genes are potent oncogenes that play a role in many human cancers

Wikipedia summary for K-Ras :

GTPase KRas also known as V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog and KRAS, is a protein that in humans is encoded by the KRAS gene.[1][2] The protein product of the normal KRAS gene performs an essential function in normal tissue signaling, and the mutation of a KRAS gene is an essential step in the development of many cancers.[3] Like other members of the Ras family, the KRAS protein is a GTPase and is an early player in many signal transduction pathways. KRAS is usually tethered to cell membranes because of the presence of an isoprenyl group on its C-terminus.

Human K-Ras Protein General Information

 

• Protein names: K-Ras
• Enzyme regulation: Alternate between an inactive form bound to K-Ras and an active form bound to K-Ras. Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by a GTPase-activating protein (K-Ras).
• Sequence length: 189 AA
• Sequence similarities: Belongs to the small GTPase superfamily. Ras family.
• Subunit structure: Interacts with PHLPP. Interacts (active GTP-bound form preferentially) with RGS14
• Subcellular location: Cell membrane; Lipid-anchor; Cytoplasmic side.
• Involvement in disease: Defects in KRAS are a cause of acute myelogenous leukemia (AML) [MIM:601626]. AML is a malignant disease in which hematopoietic precursors are arrested in an early stage of development. Ref.23 Defects in KRAS are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:607785]. JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia. It is characterized by leukocytosis with tissue infiltration and in vitro hypersensitivity of myeloid progenitors to granulocyte-macrophage colony stimulating factor.

General information above from UniProt

Function for K-Ras Protein

UniProtKB:

Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.

Genatlas:

• K-Ras is involved in the regulation of cell division as a result of its ability to relay external signals to the cell nucleus (Pubmed 20617134)
• K-Ras is not phosphorylated, it exhibits a remarkably decreased ability to stimulate proliferation in non-saturated serum conditions (Pubmed 20802526)
• K-Ras modulates mitochondrial metabolism inbcolon cancer cells by inducing HIF1A and HIF2A target genes (Pubmed 21073737)

Homology for human K-Ras

• ortholog to murine Kras
• ortholog to rattus Kras2

Phenotype Information for K-Ras

• Gene/Locus: KRAS, KRAS2, RASK2, NS
• Phenotype: Bladder cancer
  Breast cancer, somatic
  Cardiofaciocutaneous syndrom
  Gastric cancer
  Leukemia, acute myelogenous
  Lung cancer
  Pancreatic carcinoma, somatic

Phenotype Information for K-Ras from OMIM (Online Mendelian Inheritance in Man)

Drugs for K-Ras

Drugs for K-Ras from TTD (Therapeutic Targets Database)