KRAS
GeneName
KRAS
Summary
KRAS, also known as Ras or K Ras, is a small GTPase protein with a mass of 22 kDa, predominantly located in the cytoplasm and associated with various cellular membranes, including the plasma membrane and endoplasmic reticulum membrane. It plays a pivotal role in cell signalling by binding to GTP and GDP, thus acting as a molecular switch that regulates multiple biological processes such as the MAPK cascade, cytoskeleton organisation, and cell proliferation. KRAS is involved in diverse pathways, including epithelial tube branching in lung morphogenesis and neuronal differentiation, and is crucial for maintaining cellular homeostasis and responding to various extracellular signals.
Importance
KRAS is relevant to: - Cancer research, particularly in understanding oncogenic mutations that lead to uncontrolled cell growth and proliferation - Developmental biology, as it is involved in processes like cardiac muscle cell proliferation and lung morphogenesis - Neurobiology, due to its role in neuronal signalling and synaptic plasticity - Therapeutic targeting, as it represents a significant challenge in drug development for targeted therapies in KRAS-mutant cancers
Top Products
For researchers investigating KRAS, we recommend two excellent primary antibodies. The first is the well-cited monoclonal antibody, Anti-Ras antibody [4F3] (ab55391), which has garnered 39 citations, highlighting its reliability in Western blotting (WB) and flow cytometry (FC). This antibody is a trusted choice for those studying KRAS in various contexts. Additionally, we offer the recombinant antibody, Anti-KRAS antibody [EPR23474-76] (ab275876), which has been validated in knockout models and is suitable for Western blotting (WB) and immunoprecipitation (IP). With 17 citations, this product is gaining traction in the research community and provides the batch-to-batch consistency that is characteristic of recombinant antibodies. Together, these antibodies provide robust options for KRAS research.
Abcam Product Citation Summary
The data indicates that KRAS is being studied in various contexts, including its activation in mouse models and its expression in human cells related to endometriosis and transgene expression. The use of both Western blotting and immunohistochemistry suggests a focus on understanding KRAS's role in different biological processes.
Abcam Product Citation Table
Function
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).
Involvement in disease
Leukemia, acute myelogenous
AML
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.
None
The disease is caused by variants affecting the gene represented in this entry.
Leukemia, juvenile myelomonocytic
JMML
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.
None
The disease is caused by variants affecting the gene represented in this entry.
Noonan syndrome 3
NS3
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.
None
The disease is caused by variants affecting the gene represented in this entry.
Gastric cancer
GASC
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.
None
The disease is caused by variants affecting the gene represented in this entry.
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.
Cardiofaciocutaneous syndrome 2
CFC2
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.
None
The disease is caused by variants affecting the gene represented in this entry.
KRAS mutations are involved in cancer development.
Oculoectodermal syndrome
OES
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.
None
The disease is caused by variants affecting the gene represented in this entry.
Schimmelpenning-Feuerstein-Mims syndrome
SFM
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.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Acetylation at Lys-104 prevents interaction with guanine nucleotide exchange factors (GEFs).
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).
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.
(Microbial infection) Glucosylated at Thr-35 by P.sordellii toxin TcsL.
Sequence Similarities
Belongs to the small GTPase superfamily. Ras family.
Tissue Specificity
Expressed throughout the epidermis, but weakly expressed in the stratum corneum and dermis (at protein level).
Cellular localization
- Cell membrane
- Lipid-anchor
- Cytoplasmic side
- Endomembrane system
- Cytoplasm
- Isoform 2B
- Cell membrane
- Lipid-anchor
Alternative names
KRAS2, RASK2, KRAS, GTPase KRas, K-Ras 2, Ki-Ras, c-K-ras, c-Ki-ras
Database links
swissprot:P01116 entrezGene:3265 entrezGene:4893 entrezGene:3845 swissprot:P01112 swissprot:P01111 omim:164790 omim:190020 omim:190070
Other research areas
- Epigenetics
- Immuno-oncology