N-Myc

V-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog
Identifiers
Symbols	MYCN ; MODED; N-myc; NMYC; ODED; bHLHe37
External IDs	OMIM: 164840 MGI: 97357 HomoloGene: 3922 GeneCards: MYCN Gene
Gene ontology Molecular function • DNA binding • transcription factor activity, sequence-specific DNA binding • protein binding • protein dimerization activity Cellular component • chromatin • nucleus Biological process • cartilage condensation • positive regulation of mesenchymal cell proliferation • transcription, DNA-templated • regulation of transcription from RNA polymerase II promoter • positive regulation of cell death • lung development • embryonic digit morphogenesis • positive regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • embryonic skeletal system morphogenesis • negative regulation of astrocyte differentiation • branching morphogenesis of an epithelial tube • negative regulation of reactive oxygen species metabolic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4613	18109
Ensembl	ENSG00000134323	ENSMUSG00000037169
UniProt	P04198	P03966
RefSeq (mRNA)	NM_001293228	NM_008709
RefSeq (protein)	NP_001280157	NP_032735
Location (UCSC)	Chr 2: 15.94 – 15.95 Mb	Chr 12: 12.94 – 12.94 Mb
PubMed search	[1]	[2]

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.

Function

The MYCN gene is a member of the MYC family of transcription factors and encodes a protein with a basic helix-loop-helix (bHLH) domain. This protein is located in the cell nucleus and must dimerize with another bHLH protein in order to bind DNA. N-Myc is highly expressed in the fetal brain and is critical for normal brain development.

The MYCN gene has an antisense RNA, N-cym or MYCNOS, transcribed from the opposite strand which can be translated to form a protein product. N-Myc and MYCNOS are co-regulated both in normal development and in tumor cells, so it is possible that the two proteins are functionally related. It has been shown that NCYM antisense RNA encodes for a protein that has originated de novo and is specific to human and chimpanzee. This NCYM protein inhibits GSK3b and thus prevents MYCN degradation. Transgenic mice that harbor human MYCN/NCYM pair often show neuroblastomas with distant metastasis, which are atypical for normal mice. Thus NCYM represents a rare example of a de novo gene that has acquired molecular function and plays a major role in oncogenesis.

Clinical significance

Amplification and overexpression of N-Myc can lead to tumorigenesis. Excess N-Myc is associated with a variety of tumors, most notably neuroblastomas where patients with amplification of the N-Myc gene tend to have poor outcomes.

Interactions

N-Myc has been shown to interact with MAX.

N-Myc is also stabilized by aurora A which protects it from degradation. Drugs that target this interaction are under development, and are designed to change the conformation of aurora A. Conformational change in Aurora A leads to release of N-Myc, which is then degraded in a ubiquitin-dependent manner.

See also

• Myc

External links

• MYCN protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.