Neuroblastoma RAS viral oncogene homolog

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
External IDs	MGI: 97376 HomoloGene: 55661 GeneCards: NRAS
Targeted by Drug
lonafarnib[1]
Gene ontology Molecular function • nucleotide binding • protein complex binding • GTP binding Cellular component • Golgi apparatus • membrane • Golgi membrane • plasma membrane • extracellular exosome Biological process • epidermal growth factor receptor signaling pathway • stimulatory C-type lectin receptor signaling pathway • establishment of protein localization to Golgi • MAPK cascade • axon guidance • Fc-epsilon receptor signaling pathway • Ras protein signal transduction • leukocyte migration • signal transduction • small GTPase mediated signal transduction • ERBB2 signaling pathway Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	4893	18176
Ensembl	ENSG00000213281	ENSMUSG00000027852
UniProt	P01111	P08556
RefSeq (mRNA)	NM_002524	NM_010937
RefSeq (protein)	NP_002515.1	n/a
Location (UCSC)	Chr 1: 114.7 – 114.72 Mb	Chr 3: 103.06 – 103.07 Mb
PubMed search	[2]	[3]
Wikidata

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.^[4][5] 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 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.^[6]

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.^[6] eg melanoma.

As a drug target

Binimetinib (MEK162) has had a phase III clinical trial for NRAS Q61 mutant melanoma.^[7]

References

Further reading

External links

• GeneReviews/NCBI/NIH/UW entry on Noonan syndrome

PDB gallery
121p: STRUKTUR UND GUANOSINTRIPHOSPHAT-HYDROLYSEMECHANISMUS DES C-TERMINAL VERKUERZTEN MENSCHLICHEN KREBSPROTEINS P21-H-RAS  1aa9: HUMAN C-HA-RAS(1-171)(DOT)GDP, NMR, MINIMIZED AVERAGE STRUCTURE  1agp: THREE-DIMENSIONAL STRUCTURES AND PROPERTIES OF A TRANSFORMING AND A NONTRANSFORMING GLY-12 MUTANT OF P21-H-RAS  1bkd: COMPLEX OF HUMAN H-RAS WITH HUMAN SOS-1  1clu: H-RAS COMPLEXED WITH DIAMINOBENZOPHENONE-BETA,GAMMA-IMIDO-GTP  1crp: THE SOLUTION STRUCTURE AND DYNAMICS OF RAS P21. GDP DETERMINED BY HETERONUCLEAR THREE AND FOUR DIMENSIONAL NMR SPECTROSCOPY  1crq: THE SOLUTION STRUCTURE AND DYNAMICS OF RAS P21. GDP DETERMINED BY HETERONUCLEAR THREE AND FOUR DIMENSIONAL NMR SPECTROSCOPY  1crr: THE SOLUTION STRUCTURE AND DYNAMICS OF RAS P21. GDP DETERMINED BY HETERONUCLEAR THREE AND FOUR DIMENSIONAL NMR SPECTROSCOPY  1ctq: STRUCTURE OF P21RAS IN COMPLEX WITH GPPNHP AT 100 K  1gnp: X-RAY CRYSTAL STRUCTURE ANALYSIS OF THE CATALYTIC DOMAIN OF THE ONCOGENE PRODUCT P21H-RAS COMPLEXED WITH CAGED GTP AND MANT DGPPNHP  1gnq: X-RAY CRYSTAL STRUCTURE ANALYSIS OF THE CATALYTIC DOMAIN OF THE ONCOGENE PRODUCT P21H-RAS COMPLEXED WITH CAGED GTP AND MANT DGPPNHP  1gnr: X-RAY CRYSTAL STRUCTURE ANALYSIS OF THE CATALYTIC DOMAIN OF THE ONCOGENE PRODUCT P21H-RAS COMPLEXED WITH CAGED GTP AND MANT DGPPNHP  1he8: RAS G12V - PI 3-KINASE GAMMA COMPLEX  1iaq: C-H-RAS P21 PROTEIN MUTANT WITH THR 35 REPLACED BY SER (T35S) COMPLEXED WITH GUANOSINE-5'-[B,G-IMIDO] TRIPHOSPHATE  1ioz: Crystal Structure of the C-HA-RAS Protein Prepared by the Cell-Free Synthesis  1jah: H-RAS P21 PROTEIN MUTANT G12P, COMPLEXED WITH GUANOSINE-5'-[BETA,GAMMA-METHYLENE] TRIPHOSPHATE AND MAGNESIUM  1jai: H-RAS P21 PROTEIN MUTANT G12P, COMPLEXED WITH GUANOSINE-5'-[BETA,GAMMA-METHYLENE] TRIPHOSPHATE AND MANGANESE  1k8r: Crystal structure of Ras-Bry2RBD complex  1lf0: Crystal Structure of RasA59G in the GTP-bound form  1lf5: Crystal Structure of RasA59G in the GDP-bound Form  1lfd: CRYSTAL STRUCTURE OF THE ACTIVE RAS PROTEIN COMPLEXED WITH THE RAS-INTERACTING DOMAIN OF RALGDS  1nvu: Structural evidence for feedback activation by RasGTP of the Ras-specific nucleotide exchange factor SOS  1nvv: Structural evidence for feedback activation by RasGTP of the Ras-specific nucleotide exchange factor SOS  1nvw: Structural evidence for feedback activation by RasGTP of the Ras-specific nucleotide exchange factor SOS  1nvx: Structural evidence for feedback activation by RasGTP of the Ras-specific nucleotide exchange factor SOS  1p2s: H-Ras 166 in 50% 2,2,2 triflouroethanol  1p2t: H-Ras 166 in Aqueous mother liqour, RT  1p2u: H-Ras in 50% isopropanol  1p2v: H-RAS 166 in 60 % 1,6 hexanediol  1plj: CRYSTALLOGRAPHIC STUDIES ON P21H-RAS USING SYNCHROTRON LAUE METHOD: IMPROVEMENT OF CRYSTAL QUALITY AND MONITORING OF THE GTPASE REACTION AT DIFFERENT TIME POINTS  1plk: CRYSTALLOGRAPHIC STUDIES ON P21H-RAS USING SYNCHROTRON LAUE METHOD: IMPROVEMENT OF CRYSTAL QUALITY AND MONITORING OF THE GTPASE REACTION AT DIFFERENT TIME POINTS  1pll: CRYSTALLOGRAPHIC STUDIES ON P21H-RAS USING SYNCHROTRON LAUE METHOD: IMPROVEMENT OF CRYSTAL QUALITY AND MONITORING OF THE GTPASE REACTION AT DIFFERENT TIME POINTS  1q21: CRYSTAL STRUCTURES AT 2.2 ANGSTROMS RESOLUTION OF THE CATALYTIC DOMAINS OF NORMAL RAS PROTEIN AND AN ONCOGENIC MUTANT COMPLEXED WITH GSP  1qra: STRUCTURE OF P21RAS IN COMPLEX WITH GTP AT 100 K  1rvd: H-RAS COMPLEXED WITH DIAMINOBENZOPHENONE-BETA,GAMMA-IMIDO-GTP  1wq1: RAS-RASGAP COMPLEX  1xcm: Crystal structure of the GppNHp-bound H-Ras G60A mutant  1xd2: Crystal Structure of a ternary Ras:SOS:Ras*GDP complex  1xj0: Crystal Structure of the GDP-bound form of the RasG60A mutant  1zvq: Structure of the Q61G mutant of Ras in the GDP-bound form  1zw6: Crystal Structure of the GTP-bound form of RasQ61G  221p: THREE-DIMENSIONAL STRUCTURES OF H-RAS P21 MUTANTS: MOLECULAR BASIS FOR THEIR INABILITY TO FUNCTION AS SIGNAL SWITCH MOLECULES  2c5l: STRUCTURE OF PLC EPSILON RAS ASSOCIATION DOMAIN WITH HRAS  2ce2: CRYSTAL STRUCTURE ANALYSIS OF A FLUORESCENT FORM OF H-RAS P21 IN COMPLEX WITH GDP  2cl0: CRYSTAL STRUCTURE ANALYSIS OF A FLUORESCENT FORM OF H-RAS P21 IN COMPLEX WITH GPPNHP  2cl6: CRYSTAL STRUCTURE ANALYSIS OF A FLUORESCENT FORM OF H-RAS P21 IN COMPLEX WITH S-CAGED GTP  2cl7: CRYSTAL STRUCTURE ANALYSIS OF A FLUORESCENT FORM OF H-RAS P21 IN COMPLEX WITH GTP  2clc: CRYSTAL STRUCTURE ANALYSIS OF A FLUORESCENT FORM OF H-RAS P21 IN COMPLEX WITH GTP (2)  2cld: CRYSTAL STRUCTURE ANALYSIS OF A FLUORESCENT FORM OF H-RAS P21 IN COMPLEX WITH GDP (2)  2evw: Crystal structure analysis of a fluorescent form of H-Ras p21 in complex with R-caged GTP  421p: THREE-DIMENSIONAL STRUCTURES OF H-RAS P21 MUTANTS: MOLECULAR BASIS FOR THEIR INABILITY TO FUNCTION AS SIGNAL SWITCH MOLECULES  521p: THREE-DIMENSIONAL STRUCTURES OF H-RAS P21 MUTANTS: MOLECULAR BASIS FOR THEIR INABILITY TO FUNCTION AS SIGNAL SWITCH MOLECULES  5p21: REFINED CRYSTAL STRUCTURE OF THE TRIPHOSPHATE CONFORMATION OF H-RAS P21 AT 1.35 ANGSTROMS RESOLUTION: IMPLICATIONS FOR THE MECHANISM OF GTP HYDROLYSIS  621p: THREE-DIMENSIONAL STRUCTURES OF H-RAS P21 MUTANTS: MOLECULAR BASIS FOR THEIR INABILITY TO FUNCTION AS SIGNAL SWITCH MOLECULES  6q21: MOLECULAR SWITCH FOR SIGNAL TRANSDUCTION: STRUCTURAL DIFFERENCES BETWEEN ACTIVE AND INACTIVE FORMS OF PROTOONCOGENIC RAS PROTEINS  721p: THREE-DIMENSIONAL STRUCTURES OF H-RAS P21 MUTANTS: MOLECULAR BASIS FOR THEIR INABILITY TO FUNCTION AS SIGNAL SWITCH MOLECULES  821p: THREE-DIMENSIONAL STRUCTURES AND PROPERTIES OF A TRANSFORMING AND A NONTRANSFORMING GLYCINE-12 MUTANT OF P21H-RAS