Neuroblastoma RAS viral oncogene homolog

Last updated
NRAS
Protein NRAS PDB 121p.png
Available structures
PDB Ortholog search: PDBe RCSB
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
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 Mb Chr 3: 102.97 – 102.98 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/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.

Contents

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]

Related Research Articles

<span class="mw-page-title-main">Ras GTPase</span> GTP-binding proteins functioning on cell-cycle regulation

Ras, from "Rat sarcoma virus", is a family of related proteins that are expressed in all animal cell lineages and organs. All Ras protein family members belong to a class of protein called small GTPase, and are involved in transmitting signals within cells. Ras is the prototypical member of the Ras superfamily of proteins, which are all related in three-dimensional structure and regulate diverse cell behaviours.

<span class="mw-page-title-main">HRAS</span> Protein-coding gene in the species Homo sapiens

GTPase HRas, from "Harvey Rat sarcoma virus", also known as transforming protein p21 is an enzyme that in humans is encoded by the HRAS gene. The HRAS gene is located on the short (p) arm of chromosome 11 at position 15.5, from base pair 522,241 to base pair 525,549. HRas is a small G protein in the Ras subfamily of the Ras superfamily of small GTPases. Once bound to Guanosine triphosphate, H-Ras will activate a Raf kinase like c-Raf, the next step in the MAPK/ERK pathway.

<span class="mw-page-title-main">PAX3</span> Paired box gene 3

The PAX3 gene encodes a member of the paired box or PAX family of transcription factors. The PAX family consists of nine human (PAX1-PAX9) and nine mouse (Pax1-Pax9) members arranged into four subfamilies. Human PAX3 and mouse Pax3 are present in a subfamily along with the highly homologous human PAX7 and mouse Pax7 genes. The human PAX3 gene is located in the 2q36.1 chromosomal region, and contains 10 exons within a 100 kb region.

<span class="mw-page-title-main">Neurofibromin 1</span> Mammalian protein found in Homo sapiens

neurofibromatosis 1 (NF1) is a gene in humans that is located on chromosome 17. NF1 codes for neurofibromin, a GTPase-activating protein that negatively regulates RAS/MAPK pathway activity by accelerating the hydrolysis of Ras-bound GTP. NF1 has a high mutation rate and mutations in NF1 can alter cellular growth control, and neural development, resulting in neurofibromatosis type 1. Symptoms of NF1 include disfiguring cutaneous neurofibromas (CNF), café au lait pigment spots, plexiform neurofibromas (PN), skeletal defects, optic nerve gliomas, life-threatening malignant peripheral nerve sheath tumors (MPNST), pheochromocytoma, attention deficits, learning deficits and other cognitive disabilities.

<span class="mw-page-title-main">N-Myc</span> Protein-coding gene in the species Homo sapiens

N-myc proto-oncogene protein also known as N-Myc or basic helix-loop-helix protein 37 (bHLHe37), is a protein that in humans is encoded by the MYCN gene.

<span class="mw-page-title-main">KRAS</span> Protein-coding gene in humans

KRAS 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 to grow and divide (proliferate) or to mature and take on specialized functions (differentiate). It is called KRAS because it was first identified as a viral oncogene in the KirstenRAt Sarcoma virus. The oncogene identified was derived from a cellular genome, so KRAS, when found in a cellular genome, is called a proto-oncogene.

<span class="mw-page-title-main">CHEK2</span> Protein-coding gene in humans

CHEK2 is a tumor suppressor gene that encodes the protein CHK2, a serine-threonine kinase. CHK2 is involved in DNA repair, cell cycle arrest or apoptosis in response to DNA damage. Mutations to the CHEK2 gene have been linked to a wide range of cancers.

<span class="mw-page-title-main">BRAF (gene)</span> Protein-coding gene in the species Homo sapiens

BRAF is a human gene that encodes a protein called B-Raf. The gene is also referred to as proto-oncogene B-Raf and v-Raf murine sarcoma viral oncogene homolog B, while the protein is more formally known as serine/threonine-protein kinase B-Raf.

<span class="mw-page-title-main">RAB7A</span> Protein-coding gene in the species Homo sapiens

Ras-related protein Rab-7a is a protein that in humans is encoded by the RAB7A gene.

<span class="mw-page-title-main">MST1R</span> Protein-coding gene in the species Homo sapiens

Macrophage-stimulating protein receptor is a protein that in humans is encoded by the MST1R gene. MST1R is also known as RON kinase, named after the French city in which it was discovered. It is related to the c-MET receptor tyrosine kinase.

<span class="mw-page-title-main">G3BP1</span> Protein-coding gene in the species Homo sapiens

Ras GTPase-activating protein-binding protein 1 is an enzyme that in humans is encoded by the G3BP1 gene.

<span class="mw-page-title-main">KIF1B</span> Mammalian protein found in Homo sapiens

Kinesin-like protein KIF1B is a protein that in humans is encoded by the KIF1B gene.

<span class="mw-page-title-main">RRAS2</span> Protein-coding gene in the species Homo sapiens

Ras-related protein R-Ras2 is a protein that in humans is encoded by the RRAS2 gene.

<span class="mw-page-title-main">HOXC6</span> Protein-coding gene in the species Homo sapiens

Homeobox protein Hox-C6 is a protein that in humans is encoded by the HOXC6 gene. Hox-C6 expression is highest in the fallopian tube and ovary. HoxC6 has been highly expressed in many types of cancers including prostate, breast, and esophageal squamous cell cancer.

<span class="mw-page-title-main">MAPKAP1</span> Protein-coding gene in the species Homo sapiens

Target of rapamycin complex 2 subunit MAPKAP1 is a protein that in humans is encoded by the MAPKAP1 gene. As the name indicates, it is a subunit of mTOR complex 2.

<span class="mw-page-title-main">UBE4B</span> Protein-coding gene in the species Homo sapiens

Ubiquitin conjugation factor E4 B is a protein that in humans is encoded by the UBE4B gene.

<span class="mw-page-title-main">RASGRP1</span> Protein-coding gene in the species Homo sapiens

RAS guanyl-releasing protein 1 is a protein that in humans is encoded by the RASGRP1 gene.

<span class="mw-page-title-main">RREB1</span> Protein-coding gene in the species Homo sapiens

Ras-responsive element-binding protein 1 is a protein that in humans is encoded by the RREB1 gene.

<span class="mw-page-title-main">MAGEA11</span> Protein-coding gene in humans

Melanoma-associated antigen 11 is a protein that in humans is encoded by the MAGEA11 gene. It is also involved in the androgen and progesterone receptor signaling pathways.

<span class="mw-page-title-main">RAS-associated autoimmune leukoproliferative disorder</span> Medical condition

RAS-associated autoimmune leukoproliferative disorder (RALD) is a rare genetic disorder of the immune system. RALD is characterized by lymphadenopathy, splenomegaly, autoimmunity, and elevation in granulocytes and monocytes. It shares many features with autoimmune lymphoproliferative syndrome and is caused by somatic mutations in NRAS or KRAS. This was first described by investigators João Oliveira and Michael Lenardo from the National Institutes of Health.

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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