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FLASH GENE
Symbol MYCN contributors: mct/pgu - updated : 08-04-2015
HGNC name v-myc myelocytomatosis viral related oncogene, neuroblastoma derived (avian)
HGNC id 7559
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
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 2613 - 464 - 2008 18165268
    3 - 3045 - 464 - 2008 18165268
    3 - 2736 - 112 - 2008 18165268
    2 - 1829 - 253 - 2008 18165268
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticthymus   highly
    Cardiovascularheart    
    Nervousbrain   highly
    Reproductivefemale systemovary   
    Respiratorylung    
    Visualeye    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    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
  • 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)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein 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
    SystemTypeDisorderPubmed
    cancerbrainglioma/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