Neuroblastoma RAS viral oncogene homolog

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.

NRAS
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3CON, 2N9C
Identifiers
Aliases	NRAS, ALPS4, CMNS, N-ras, NCMS, NRAS1, NS6, Neuroblastoma RAS viral oncogene homolog, NRAS proto-oncogene, GTPase
External IDs	OMIM: 164790; MGI: 97376; HomoloGene: 55661; GeneCards: NRAS; OMA:NRAS - orthologs
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p13.2 Start 114,704,469 bp[1] End 114,716,771 bp[1]
Gene location (Mouse) Chr. Chromosome 3 (mouse)[2] Band 3 F2.2|3 45.25 cM Start 102,965,601 bp[2] End 102,975,230 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gingival epithelium epithelium of nasopharynx secondary oocyte amniotic fluid mucosa of colon mucosa of sigmoid colon germinal epithelium skin of thigh ganglionic eminence parietal pleura Top expressed in tail of embryo genital tubercle zygote lactiferous gland sciatic nerve yolk sac ventricular zone corneal stroma epithelium of lens medial ganglionic eminence More reference expression data BioGPS n/a
Gene ontology Molecular function nucleotide binding protein-containing complex binding GTP binding GTPase activity protein binding Cellular component Golgi apparatus membrane Golgi membrane plasma membrane extracellular exosome tertiary granule membrane Biological process epidermal growth factor receptor signaling pathway stimulatory C-type lectin receptor signaling pathway MAPK cascade axon guidance Fc-epsilon receptor signaling pathway Ras protein signal transduction leukocyte migration signal transduction ERBB2 signaling pathway neutrophil degranulation positive regulation of endothelial cell proliferation Sources:Amigo / QuickGO
Orthologs Species Human Mouse 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 Mb Chr 3: 102.97 – 102.98 Mb PubMed search [3] [4]
Wikidata
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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]