KRAS

Target id: 2824

Nomenclature: KRAS

Family: RAS subfamily

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for KRAS in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 188 12p12.1 KRAS KRAS proto-oncogene, GTPase
Mouse - 188 6 G2 Kras Kirsten rat sarcoma viral oncogene homolog
Rat - 188 4q44 Kras KRAS proto-oncogene, GTPase
Gene and Protein Information Comments
Human KRAS has two isoforms. The prediminant isoform (b) is the 188 amino acid protein (NP_004976), the shorter isoform (a) is 189 amino acids long.
Previous and Unofficial Names
KRAS2 | v-Ki-ras2 | v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog | Kirsten rat sarcoma viral oncogene homolog | Kirsten rat sarcoma viral oncogene
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
lonafarnib Hs Inhibition 8.3 pIC50 7
pIC50 8.3 (IC50 5.2x10-9 M) [7]
Description: Measuring inhibition of farnesylation of KRAS4B by human farnesyltransferase
Clinically-Relevant Mutations and Pathophysiology
Disease:  Acute myeloid leukemia
Synonyms: Acute myelogenous leukemia
Disease Ontology: DOID:9119
OMIM: 601626
Orphanet: ORPHA519
Disease:  Bladder cancer
Disease Ontology: DOID:11054
OMIM: 109800
Disease:  Breast cancer
Disease Ontology: DOID:1612
OMIM: 114480
Disease:  Cardiofaciocutaneous syndrome 2; CFC2
Synonyms: Cardiofaciocutaneous syndrome [Orphanet: ORPHA1340]
OMIM: 615278
Orphanet: ORPHA1340
Disease:  Familial pancreatic carcinoma
Synonyms: Pancreatic cancer [OMIM: 260350]
Pancreatic carcinoma [Disease Ontology: DOID:4905]
Disease Ontology: DOID:4905
OMIM: 260350
Orphanet: ORPHA1333
Disease:  Gastric cancer, hereditary diffuse; HDGC
OMIM: 137215
Disease:  Juvenile myelomonocytic leukemia; JMML
Disease Ontology: DOID:0050458
OMIM: 607785
Orphanet: ORPHA86834
Disease:  Lung cancer
Disease Ontology: DOID:1324
OMIM: 211980
Disease:  Noonan syndrome 3; NS3
Synonyms: Noonan syndrome [Orphanet: ORPHA648] [Disease Ontology: DOID:3490]
Disease Ontology: DOID:3490
OMIM: 609942
Orphanet: ORPHA648
Disease:  Schimmelpenning-Feuerstein-Mims syndrome; SFM
Synonyms: Linear nevus sebaceus syndrome [Orphanet: ORPHA2612]
OMIM: 163200
Orphanet: ORPHA2612
General Comments
Somatic activating mutations in KRAS are extensively found in leukemias [3,11], colon cancer [4,8], pancreatic cancer [1,5] and lung cancer [6,10]. The single amino acid substitution replacing glycine at position 12 with cysteine is a common oncogenic KRAS mutation, as are substitutions at Gly12 and Glu61 [9]. The search for small molecule inhibitors of activated KRAS with anticancer activity is intense [2].

References

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1. Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M. (1988) Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell53 (4): 549-54. [PMID:2453289]

2. Baines AT, Xu D, Der CJ. (2011) Inhibition of Ras for cancer treatment: the search continues. Future Med Chem3 (14): 1787-808. [PMID:22004085]

3. Braun BS, Shannon K. (2008) Targeting Ras in myeloid leukemias. Clin. Cancer Res.14 (8): 2249-52. [PMID:18413813]

4. Burmer GC, Loeb LA. (1989) Mutations in the KRAS2 oncogene during progressive stages of human colon carcinoma. Proc. Natl. Acad. Sci. U.S.A.86 (7): 2403-7. [PMID:2648401]

5. Collins MA, Pasca di Magliano M. (2013) Kras as a key oncogene and therapeutic target in pancreatic cancer. Front Physiol4: 407. [PMID:24478710]

6. Cooper WA, Lam DC, O'Toole SA, Minna JD. (2013) Molecular biology of lung cancer. J Thorac Dis5 Suppl 5: S479-90. [PMID:24163741]

7. Liu M, Bryant MS, Chen J, Lee S, Yaremko B, Lipari P, Malkowski M, Ferrari E, Nielsen L, Prioli N et al.. (1998) Antitumor activity of SCH 66336, an orally bioavailable tricyclic inhibitor of farnesyl protein transferase, in human tumor xenograft models and wap-ras transgenic mice. Cancer Res.58 (21): 4947-56. [PMID:9810004]

8. Rasool S, Rasool V, Naqvi T, Ganai BA, Shah BA. (2014) Genetic unraveling of colorectal cancer. Tumour Biol.35 (6): 5067-82. [PMID:24573608]

9. Spiegel J, Cromm PM, Zimmermann G, Grossmann TN, Waldmann H. (2014) Small-molecule modulation of Ras signaling. Nat. Chem. Biol.10 (8): 613-22. [PMID:24929527]

10. Tam IY, Chung LP, Suen WS, Wang E, Wong MC, Ho KK, Lam WK, Chiu SW, Girard L, Minna JD et al.. (2006) Distinct epidermal growth factor receptor and KRAS mutation patterns in non-small cell lung cancer patients with different tobacco exposure and clinicopathologic features. Clin. Cancer Res.12 (5): 1647-53. [PMID:16533793]

11. Yoshida N, Doisaki S, Kojima S. (2012) Current management of juvenile myelomonocytic leukemia and the impact of RAS mutations. Paediatr Drugs14 (3): 157-63. [PMID:22480363]

Contributors

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How to cite this page

Elena Faccenda.
RAS subfamily: KRAS. Last modified on 13/08/2015. Accessed on 21/09/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2824.