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FLASH GENE

Symbol

MYCN

contributors: mct/pgu - updated : 08-04-2017

HGNC name	v-myc myelocytomatosis viral related oncogene, neuroblastoma derived (avian)
HGNC id	7559

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	NBL2 neuroblastoma
Location	2p24.3      Physical location : 16.080.682 - 16.087.128
Synonym name	N-myc proto-oncogene protein
	pp65/67
	oncogene NMYC
	neuroblastoma MYC oncogene
	class E basic helix-loop-helix protein 37
	neuroblastoma-derived v-myc avian myelocytomatosis viral related oncogene
Synonym symbol(s)	NMYC, N-myc, bHLHe37, MODED, ODED

DNA

TYPE	functioning gene
STRUCTURE	6.57 kb     3 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	cytosine-phosphate-guanine/HTF
	Binding site   transcription factor
text structure	two GC-rich motifs and a CT box, regions for potential transcription factor interaction (Sp1 consensus motifs)
	an ATG start codon in exon 2

MAPPING

cloned

Y

linked

Y

status

confirmed

Map	pter - NAG - DDX1 - MYCN - cen

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005378 3 - 2613 NP_005369 - 464 - 2008 18165268 NM_001293228 3 - 3045 NP_001280157 - 464 - 2008 18165268 NM_001293233 3 - 2736 NP_001280162 - 112 - 2008 18165268 NM_001293231 2 - 1829 NP_001280160 - 253 - 2008 18165268

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol blood / hematopoietic thymus       highly Cardiovascular heart         Nervous brain       highly Reproductive female system ovary       Respiratory lung         Visual eye

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text	fetal development

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	basic helix-loop-helix (bHLH)
	leucine zipper domains

conjugated

PhosphoP

mono polymer

heteromer , dimer

HOMOLOGY

interspecies	homolog to murine Mycn (85.7pc)
	homolog to rattus Mycn (86.1pc)

Homologene

FAMILY	MYC proto-oncoprotein family
	basic helix-loop-helix (BHLH) family of transcription factors
	BHLH-ZIP subfamily

CATEGORY

transcription factor , protooncogene

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
	intracellular,nucleus,chromatin/chromosome
text	MYCN accumulates at spindle poles by GSK3B phosphorylation during mitosis of neuroblastoma cells

basic FUNCTION	playing a role in cell growth and/or maintenance
	may function as a transcription factor
	activating a core set of miRNAs for cooperative repression of common transcriptional programs related to disease aggessiveness
	playing a paradoxical role in driving cellular proliferation and inducing apoptosis
	transcriptionally upregulating TP53 in neuroblastoma and using TP53 to mediate a key mechanism of apoptosis
	amplification may disrupt estrogen signaling sensitivity through deregulation of ESR1, thereby preventing the normal induction of neuroblast differentiation
	contributes to its own expression by forming a positive auto-regulatory loop in neuroblastoma cells
	dual role of MYCN, namely that of classical transcription factor affecting the activity of individual genes and that of mediator of global chromatin structure
	may have a role in regulating livin expression in neuroblastoma
	regulates growth, morphogenesis, and pattern formation during the development of the inner ear
	acts as a direct repressor of the CDKL5 promoter
	functional axis between MYCN and CDKL5 governing both neuron proliferation rate and differentiation
	MYCN induces genes functioning in cell cycle and DNA repair while repressing neuronal differentiation genes
	MYCN, PIGV and UPF3B regulate likely synapse development

CELLULAR PROCESS	cell life, proliferation/growth
	nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	heterodimerizing with MAX and BHLH proteins
	LIN28B–MIRLET7A1–MYCN signaling blocked differentiation of normal neuroblasts and neuroblastoma cells

INTERACTION

DNA	binding directly to BMI1 promoter

RNA

small molecule

protein	binding to PAX7 and FOX01A (concomitant amplification)
	modulating MDM2 levels in neuroblastoma cells
	interacting with KDM5A, KDM5B and HUWE1
	interaction with HUWE1 (ubiquitin ligase HUWE1 operates upstream of the MYCN-DLL3-NOTCH1 pathway to control neural stem cell activity and promote neurogenesis)
	directly associated with its regulatory motif (E-box) within the putative BIRC7 promoter
	acts directly to repress NTRK1 and NGFR gene transcription
	GSTP1 is a direct transcriptional target of MYCn in neuroblastoma cells
	ALK stimulates initiation of transcription of the MYCN gene
	MYCN acts as a direct repressor of the CDKL5 promoter
	SIRT2 enhanced MYCN and MYC protein stability and promoted cancer cell proliferation
	cooperation between MYCN and BIRC5 may be important in the genesis of several cancers
	MYCN repressed KDM5B expression by direct binding to the Sp1-binding site-enriched region of the KDM5B gene promoter, and cell proliferation assays showed that transcriptional repression of KDM5B reduced neuroblastoma cell proliferation
	TRIM32 interacted with MYCN at spindle poles during mitosis, facilitating proteasomal degradation of MYCN at spindle poles and inducing Asymmetric cell division (ACD)
	SULF2 is a novel positive regulator of neuroblastoma pathogenicity that contributes to MYCN oncogenicity
	MYCN bound directly to E-boxes within the SKP2 promoter and induced transcriptional activity which was decreased by the removal of MYCN and E-box mutation
	MYCN was found to physically interact with and recruit KDM4B
	OTX2 is a crucial target of MYCN during inner ear development, and MYCN may directly regulate OTX2
	DDX21 induces CEP55 expression, MYCN-amplified neuroblastoma cell proliferation and tumorigenesis

cell & other

REGULATION

activated by

SHH signaling

repressed by

MIR34A

Other

MYCN protein activates its own promoter activity in a dose-dependent manner

ASSOCIATED DISORDERS

corresponding disease(s)

ODED , NBL2

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   amplification     in neuroblastoma, amplification is associated with rapid tumor progression and poor prognosis tumoral   amplification     in tumors with MYCN amplification and low TPX2 index, a favorable outcome whereas in tumors with normal MYCN copy number and high TPX2 index, the prognosis is extremely poor tumoral         copy number gain is relatively common in Wilms' tumor tumoral   amplification     in neuroblastoma tumoral germinal mutation     gain of function MYCN gain is a germline aberration, with a significant role for MYCN dysregulation in the molecular biology of Wilms tumour tumoral     --over   frequently overexpressed in pediatric T-ALL

Susceptibility

Variant & Polymorphism

Candidate gene	can drive medulloblastoma (initiation, progression and maintenance) independently of SHH
Marker
Therapy target
	System Type Disorder Pubmed cancer brain glioma/neuroblstoma MYCN expression can be reduced by inhibiting the activity of ALK, suggesting a promising therapeutic approach for the treatment of neuroblastoma patients harbouring MYCN and ALK genes amplification or ALK mutations

ANIMAL & CELL MODELS

in N-myc mouse mutants, loss of the lateral canal, fusion of the cochlea with the sacculus and utriculus, and stunted outgrowth of the cochlea