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FLASH GENE
Symbol NDN contributors: mct/npt - updated : 19-12-2018
HGNC name necdin, MAGE family member
HGNC id 7675
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)