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FLASH GENE
Symbol NDN contributors: mct/npt - updated : 19-12-2018
HGNC name necdin, MAGE family member
HGNC id 7675
Corresponding disease
PWS Prader-Willi syndrome
Location 15q11.2      Physical location : 23.930.561 - 23.932.450
Synonym name
  • necdin
  • Prader-Willi syndrome chromosome region
  • necdin homolog
  • necdin, melanoma antigen (MAGE) family member
  • necdin-like protein
    • Synonym symbol(s) NECDIN, HsT16328, PWCR
    DNA
    TYPE functioning gene
    SPECIAL FEATURE
    text associated with a 5'differentiated methylated region (DMR)
    STRUCTURE 1.89 kb     1 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status confirmed
    Map maps to the Prader–Willi syndrome (PWS ) chromosome region
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    1 - 1897 - 321 - 2004 15247330
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivesalivary gland   highly
    Hearing/Equilibriumear   highly
    Nervousbrain     Homo sapiens
    Reproductivefemale systemovary  highly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervousperipherous    Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Homo sapiens
    Reproductiveepithelial cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period perinatal, pregnancy
    Text placenta, expressed in satellite cell-derived myogenic precursors during perinatal growth (Deponti 2007)
    IMPRINTING maternally
    text
  • maternally imprinted, paternally expressed
  • maternally imprinted gene consistently expressed in normal ovarian epithelium, is dramatically downregulated in the majority of ovarian cancers
    • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • highly conserved MAGE homology domain
  • C-terminus of CYS1 and both termini of NDN are required for their mutual interaction
    • HOMOLOGY
    Homologene
    FAMILY
  • MAGE family protein
    • CATEGORY signaling growth factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • post mitotic neuron-specific growth suppressor with TP53 and modulating its function
  • modulating gene transcription via the GN box that is potentially recognized by GC box-targeting Sp family members
  • mediating intracellular processes essential for neurite outgrowth
  • can be a novel negative regulator of HIF-1alpha stability via the direct interaction
  • in muscle, increases myogenin expression, accelerates differentiation, and counteracts myoblast apoptosis, and have a function in skeletal muscle important in muscle regeneration (Deponti (2007)
  • may activate GNRH1 gene expression by preventing repression of GNRH1 gene expression by MSX1, MSX2 (Miller 2009)
  • tumor suppressor gene (which may have implications for monitoring of PWS patients) (Chapman 2009)
  • NDN promotes tangential migration of neocortical GABAergic interneurons during mammalian forebrain development
  • is a key protein regulating polarization of the cytoskeleton during development
  • role for necdin in inhibiting adipogenesis
  • functions as a molecular switch in adult hematopoiesis, acting in a TP53-like manner to promote hematopoietic stem cells (HSCs) quiescence in the steady state, but suppressing TP53-dependent apoptosis in response to genotoxic stress
  • is responsible for the maintenance of CCAR1 protein levels, by implementing its ubiquitination and degradation through the proteasome
  • pleiotropic protein that promotes differentiation and survival of mammalian neurons
  • suppresses likely PIAS1 both by inhibiting SUMO E3 ligase activity and by promoting ubiquitin-dependent degradation
  • is an imprinted tumor suppressor gene which affects cancer cell motility, invasion and growth and that its loss of function in ovarian cancer can be caused by both genetic and epigenetic mechanisms
  • is a key regulator of cell differentiation in various tissues, including neuronal, adipose, and muscular tissues
  • plays likely roles in cellular differentiation, proliferation and death in bone tissue
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with MAGEB1 and FEZ1 for centrosome -mediated cytoskeletal rearrangement after neuronal differentiation and for axonal outgrowth
  • interacting with BBS4 and MAGEB1
  • interaction with HIF-1alpha (reduces the transcriptional activity of HIF-1 under hypoxia)
  • interacting with NUCB2 (necdin with NUCB2 might be involved in Ca(2+) homeostasis in neuronal cytoplasm)
  • NDN and MAGEH1, are interactors for the intracellular domain of NGFR and the interaction is enhanced by ligand stimulation
  • interacting with ARNT2 (NDN regulates neuronal function and hypoxic response by regulating the activities of the ARNT2:SIM1 and ARNT2:HIF1alpha dimers, respectively)
  • key regulator of GNRH1 gene expression (Miller 2009)
  • interaction between necdin and the E1A-like inhibitor of differentiation (EID1) (promotes myoblast differentiation at least in part by relieving the inhibitory effect of EID1) (Bush 2008)
  • NDN is implicated through the TNFRSF1A pathway in the developmental death of motoneurons
  • NDN exerts its pro-survival activity by counteracting the action of the pro-apoptotic protein Cell Cycle Apoptosis Regulatory Protein (CCAR1/CARP1)
  • physical interaction with both NDN and CYS1 and the MYC P1 promoter, as well as between these proteins
  • NDN bound to PIAS1 central domains that are highly conserved among PIAS family proteins and suppressed PIAS1-dependent sumoylation of the substrates STAT1 and PML
  • expression of GNAO1 significantly augmented NDN-mediated cellular responses, such as proliferation and differentiation
  • NDN is a potent PPARGC1A stabilizer that promotes mitochondrial biogenesis via PPPARGC1A in mammalian neurons
  • NDN binds to the GN box in the promoter of LRP6 to attenuate LRP6 transcription and inhibit the Wnt signaling pathway in colorectal cancer
  • modulates osteogenic cell differentiation by regulating DLX5 and MAGED1
    • cell & other
    REGULATION
    Other oxygen tension regulates the necdin protein level in Neural stem cells (NSCs) through HIF2A-mediated proteasomal degradation to modulate their proliferation and apoptosis
    ASSOCIATED DISORDERS
    corresponding disease(s) PWS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional        
    during development likely contributes to the hypogonadotrophic hypogonadal phenotype in individuals with PWS (Miller 2009)
    constitutional   deletion    
    disturbs the migration of serotonin (5-HT) neuronal precursors, leading to altered global serotonergic neuroarchitecture and increased spontaneous firing of 5-HT neurons
    constitutional     --over  
    during osteoblast differentiation
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target cancer therapeutic target (Chapman 2009)
    ANIMAL & CELL MODELS
  • NDN knockout mouse model(Lee,05)with defects seen in PWS patients
  • Necdin-deficient mice display early post-natal lethality with variable penetrance
  • Necdin-deficient mouse is the only model that reproduces the respiratory phenotype of PWS (central apnea and blunted response to respiratory challenges)