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FLASH GENE

Symbol

NDN

contributors: mct/npt - updated : 19-12-2018

HGNC name	necdin, MAGE family member
HGNC id	7675

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002487 1 - 1897 NP_002478 - 321 - 2004 15247330

EXPRESSION

Type

widely

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 Digestive salivary gland       highly Hearing/Equilibrium ear       highly Nervous brain         Homo sapiens Reproductive female system ovary     highly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous peripherous       Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Nervous neuron Homo sapiens Reproductive epithelial 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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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)