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FLASH GENE
Symbol NDRG1 contributors: mct - updated : 31-01-2016
HGNC name N-myc downstream regulated 1
HGNC id 7679
Corresponding disease
CMT4D Charcot-Marie-tooth disease, type 4D
Location 8q24.22      Physical location : 134.249.413 - 134.309.547
Synonym name
  • nickel-specific induction protein Cap43
  • protein regulated by oxygen-1
  • tunicamycin-responsive protein
  • differentiation-related gene
  • reducing agents and tunicamycin-responsive protein
  • Synonym symbol(s) RTP, NDR1, CAP43, DRG4, RIT42, TARG1, PROXY1, GC4, DRG1, NMSL, TDD5, HMSNL
    DNA
    TYPE functioning gene
    STRUCTURE 60.13 kb     16 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter (TATA box)
    cytosine-phosphate-guanine/HTF
    Binding site   enhancer
    text structure
  • promoter region contains a TP53 binding site that confers p53-dependent transcriptional activation via a heterologous reporter
  • can be indirectly transcriptionally down-regulated by Myc via interaction with the NDRG1 core promoter
  • MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    text both variants 1 and 2 encode the same protein
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    16 splicing 3520 42.7 394 - 2004 15377670
    16 splicing 3123 42.7 394 - 2004 15377670
    using an alternate splice site in the 5' UTR
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouthtongue  highly
     pharynx   highly
    Lymphoid/Immunethymus   highly
    Nervousbrain   moderately
    Reproductivemale systemprostate  moderately
    Respiratorylung    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    Nervousperipherous   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymphocyte
    Nervousastrocyte
    Nervousoligodendrocyte
    NervousPurkinje cell
    NervousSchwann cell
    cell lineage
    cell lines most cancer cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text brain
    PROTEIN
    PHYSICAL PROPERTIES Hydrophilic
    STRUCTURE
    motifs/domains
  • three repeated highly hydrophilic amino acid sequence motifs at C terminus
  • a putative phosphopantotheine binding site
  • HOMOLOGY
    interspecies homolog to rattus Ndrg1 (93.4 pc)
    homolog to murine Ndrg1 (93.7 pc)
    Homologene
    FAMILY
  • alpha/beta hydrolase superfamily
  • N-myc downregulated gene (NDRG) family
  • CATEGORY signaling
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus
    text
  • localized in the cytoplasme of myelinating Schwann cells and oligodendrocytes, and in basolateral membranes of gut lumen surface epithelial cells
  • predominantly cytosolic
  • basic FUNCTION
  • TP53-regulated gene, involved in growth arrest, cell differentiation and playing a growth inhibitory role
  • playing mainly a crucial function in the development and/or maintenance of peripheral nerves
  • mast cell maturation-associated inducible protein that allows the cells to be susceptible to extracellular stimuli leading to degranulation
  • playing a necessary but not sufficient role for TP53-mediated caspase activation and apoptosis
  • playing a putative role in the general mechanisms of HDL-mediated cholesterol transport
  • involbed in stress responses, hormone responses, cell growth, and differentiation
  • intracellular protein associated with stress response, cell growth, and differentiation
  • may play a partially redundant role in specific cells in the brain
  • nickel- and calcium-inducible gene that plays important roles in the primary growth of malignant tumors, as well as in invasion and metastasis, most likely through its ability to induce cellular differentiation
  • may play an inhibitory role during the development of glioma and may be a potential prognosis predictor of glioma
  • importance of NDRG1 as a growth control gene in breast tissue
  • differentiation-related gene that plays important roles in cell differentiation, organ formation, and embryonic development
  • plays a significant role in invasion and metastasis of cancer
  • up-regulated CD82 expression through modulation of ATF3 signaling in prostate cancer cells
  • involved in tumor adaptation to reoxygenation
  • is an iron-regulated metastasis suppressor which is up-regulated by iron depletion and may be involved in the epithelial-mesenchymal transition (EMT)
  • is involved in the EMT through the SMAD and Wnt pathways
  • SGK1 and NDRG1 participate in the regulation of NFKB1 signaling and maturation of dendritic cells (DCs)
  • CELLULAR PROCESS cell life, differentiation
    cell life, proliferation/growth
    cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    text
  • differentiation of Schwann cells
  • mast cell activation
  • PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with APO A-I and A-II
  • binding to phosphopantetheine
  • TBX2 targets NDRG1 through a previously undescribed mechanism involving the recruitment of early growth response 1 (EGR1)
  • CD82 is a functional downstream target of the NDRG1 pathway
  • upregulates neural precursor cell expressed developmentally downregulated 4-like (NEDD4L) and GLI-similar-3 (GLIS3)
  • NDRG1 is important to maintain the integrity of airway epithelial barrier through CLDN9 expression
  • cell & other
    REGULATION
    activated by strongly up-regulated by chemical iron chelators and hypoxia
    induced by nickel (Ni2+ compounds), homocysteine, 2-mercaptoethanol and tunicamycin
    inhibited by VHL (von Hippel-Lindau tumor suppressor protein) in renal cancer cells
    repressed by both N-Myc and c-Myc via interaction with the core promoter
    Phosphorylated by the protein kinase SGK1, and is temporally and spatially controlled during the cell cycle, suggesting a role for NDRG1 in successful mitosis
    ASSOCIATED DISORDERS
    corresponding disease(s) CMT4D
    related resource Mutation Database of Inherited Peripheral Neuropathies
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in colorectal neoplasmand in renal carcinoma
    tumoral     --over  
    associated with angiogenesis and may be a poor prognostic indicator in women with cervical adenocarcinoma
    tumoral fusion      
    NDRG1-ERG fusion in prostate carcinoma is predicted to encode a chimeric protein
    tumoral     --low  
    in glioma
    constitutional     --over  
    led to decreased expression of the Wnt-responsive gene, CCND1 which drives cell cycle progression
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker could be developed as a marker contributing to diagnosis and evaluating prognosis in gastric cancer
    Therapy target
    SystemTypeDisorderPubmed
    cancerdigestivestomach
    potential therapeutic target of gastric cancer
    ANIMAL & CELL MODELS
    being up-regulated in N-Myc knockout mouse embryos