Neuroblastoma RAS viral oncogene homolog

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NRAS
Protein NRAS PDB 121p.png
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesNRAS, ALPS4, CMNS, N-ras, NCMS, NRAS1, NS6, Neuroblastoma RAS viral oncogene homolog, NRAS proto-oncogene, GTPase
External IDsMGI: 97376 HomoloGene: 55661 GeneCards: NRAS
Gene location (Human)
Chromosome 1 (human)
Chr.Chromosome 1 (human)[1]
Chromosome 1 (human)
Genomic location for NRAS
Genomic location for NRAS
Band1p13.2Start114,704,469 bp[1]
End114,716,894 bp[1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_002524

NM_010937

RefSeq (protein)

NP_002515

n/a

Location (UCSC)Chr 1: 114.7 – 114.72 MbChr 3: 103.06 – 103.07 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

NRAS is an enzyme that in humans is encoded by the NRAS gene. It was discovered by a small team of researchers led by Robin Weiss at the Institute of Cancer Research in London.[5][6] It was the third RAS gene to be discovered, and was named NRAS, for its initial identification in human neuroblastoma cells.

Function[edit]

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 and KRAS), 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 2Kb and 4.3Kb. The difference between the two transcripts is a simple extension through the termination site of the 2Kb transcript. The N-ras gene consists of seven exons (-I, I, II, III, IV, V, VI). The smaller 2Kb transcript contains the VIa exon, and the larger 4.3Kb 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.[7]

Mutations[edit]

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[7] e.g. melanoma.

As a drug target[edit]

Binimetinib (MEK162) has had a phase III clinical trial for NRAS Q61 mutant melanoma.[8]

References[edit]

Further reading[edit]

External links[edit]