NRAS is an
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
that in humans is encoded by the ''NRAS''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
. It was discovered by a small team of researchers led by
Robin Weiss at the
Institute of Cancer Research
The Institute of Cancer Research (the ICR) is a public research institute and a member institution of the University of London in London, United Kingdom, specialising in oncology. It was founded in 1909 as a research department of the Royal Ma ...
in London.
It was the third ''RAS'' gene to be discovered, and was named ''NRAS'', for its initial identification in human
neuroblastoma
Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the neck, chest, abdomen, or spine. Symptoms may include bone pain, a lump in ...
cells.
Function
The N-ras proto-oncogene is a member of the
Ras gene family. It is mapped on chromosome 1, and it is activated in HL60, a promyelocytic leukemia line. The order of nearby genes is as follows: cen—CD2—NGFB—NRAS—tel.
The mammalian Ras gene family consists of the Harvey and Kirsten Ras genes (''
HRAS
GTPase HRas, from "Harvey Rat sarcoma virus", also known as transforming protein p21 is an enzyme that in humans is encoded by the gene. The ''HRAS'' gene is located on the short (p) arm of chromosome 11 at position 15.5, from base pair 522,241 ...
'' and ''
KRAS
''KRAS'' ( Kirsten rat sarcoma virus) is a gene that provides instructions for making a protein called K-Ras, a part of the RAS/MAPK pathway. The protein relays signals from outside the cell to the cell's nucleus. These signals instruct the cell ...
''), an inactive pseudogene of each (c-Hras2 and c-Kras1) and the N-Ras gene. They differ significantly only in the C-terminal 40 amino acids. These Ras genes have GTP/GDP binding and GTPase activity, and their normal function may be as G-like regulatory proteins involved in the normal control of cell growth.
The N-Ras gene specifies two main transcripts of 2 kb and 4.3 kb. The difference between the two transcripts is a simple extension through the termination site of the 2 kb transcript. The N-Ras gene consists of seven
exon
An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequen ...
s (-I, I, II, III, IV, V, VI). The smaller 2 kb transcript contains the VIa exon, and the larger 4.3 kb transcript contains the VIb exon which is just a longer form of the VIa exon. Both transcripts encode identical proteins as they differ only the 3′ untranslated region.
Mutations
Mutations which change amino acid residues 12, 13 or 61 activate the potential of N-ras to transform cultured cells and are implicated in a variety of human tumors
e.g.
melanoma
Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...
.
As a drug target
Binimetinib
Binimetinib, also known as Mektovi and ARRY-162, is an anti-cancer small molecule that was developed by Array Biopharma to treat various cancers. Binimetinib is a selective inhibitor of MEK, a central kinase in the tumor-promoting MAPK pathway. ...
(MEK162) has had a phase III clinical trial for ''NRAS'' Q61 mutant
melanoma
Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...
.
[Study Comparing the Efficacy of MEK162 Versus Dacarbazine in Unresectable or Metastatic NRAS Mutation-positive Melanoma]
/ref>
References
Further reading
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External links
GeneReviews/NCBI/NIH/UW entry on Noonan syndrome
{{protein-stub
Oncogenes