NRAS
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 IDsOMIM: 164790 MGI: 97376 HomoloGene: 55661 GeneCards: NRAS
Orthologs
SpeciesHumanMouse
Entrez

4893

18176

Ensembl

ENSG00000213281

ENSMUSG00000027852

UniProt

P01111

P08556

RefSeq (mRNA)

NM_002524

NM_010937
NM_001368638

RefSeq (protein)

NP_002515

n/a

Location (UCSC)Chr 1: 114.7 – 114.72 MbChr 3: 102.97 – 102.98 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

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 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 exons (-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.[7]

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[7] e.g. melanoma.

As a drug target

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

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000213281 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000027852 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Marshall CJ, Hall A, Weiss RA (September 1982). "A transforming gene present in human sarcoma cell lines". Nature. 299 (5879): 171–3. Bibcode:1982Natur.299..171M. doi:10.1038/299171a0. PMID 6287287. S2CID 4342747.
  6. Shimizu K, Goldfarb M, Perucho M, Wigler M (January 1983). "Isolation and preliminary characterization of the transforming gene of a human neuroblastoma cell line". PNAS. 80 (2): 383–7. Bibcode:1983PNAS...80..383S. doi:10.1073/pnas.80.2.383. PMC 393381. PMID 6300838.
  7. 1 2 "Entrez Gene: NRAS neuroblastoma RAS viral (v-ras) oncogene homolog".
  8. Study Comparing the Efficacy of MEK162 Versus Dacarbazine in Unresectable or Metastatic NRAS Mutation-positive Melanoma

Further reading


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