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FLASH GENE
Symbol NEUROD1 contributors: shn/pgu/mct - updated : 08-01-2014
HGNC name neurogenic differentiation 1
HGNC id 7762
Corresponding disease
MODY6 maturity onset diabetes of the young, type VI
Location 2q31.3      Physical location : 182.541.194 - 182.545.381
Synonym name
  • beta-cell E-Box transactivator 2
  • basic helix-loop-helix transcription factor
  • neurogenic helix-loop-helix protein NEUROD
  • class A basic helix-loop-helix protein 3
  • Synonym symbol(s) NEUROD, BETA2, BHF1, NORF, NIDDM, bHLHa3, MODY6
    DNA
    TYPE functioning gene
    STRUCTURE 4.19 kb     2 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map cen - D2S384 - D2S2310 - NEUROD1 - D2S364 - D2S350 - qter
    Physical map
    DKFZp451M2119 2q31.2-q31.3 hypothetical protein DKFZp451M2119 AGPS 2q33 alkylglycerone phosphate synthase FLJ30990 2q31.3 hypothetical protein FLJ30990 FLJ13946 2q31.3 hypothetical protein FLJ13946 PDE11A 2q31 phosphodiesterase 11A HCP9 2q31.2 cytochrome c, somatic pseudogene DRB1 2q31.3 developmentally regulated RNA-binding protein 1 OSBPL6 2q31-q32.1 oxysterol binding protein-like 6 PRKRA 2q31.2 protein kinase, interferon-inducible double stranded RNA dependent activator NUDCP2 2q31 nuclear distribution gene C homolog (A. nidulans) pseudogene 2 FKBP7 2q31.2 FK506 binding protein 7 PLEKHA3 2q31.2 pleckstrin homology domain containing, family A (phosphoinositide binding specific) member 3 TTN 2q24.3-q31 titin FLJ39502 2q31.3 hypothetical protein FLJ39502 DKFZp434O0515 FLJ25270 LOC389065 2 similar to RIKEN cDNA B830010L13 gene LOC391466 2 similar to dim1 KIAA1604 2q32.1 KIAA1604 protein UBE2E3 2q32.1 ubiquitin-conjugating enzyme E2E 3 (UBC4/5 homolog, yeast) ITGA4 2q31-q32 integrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor) LOC151274 2q32.1 similar to Ceramide kinase (Acylsphingosine kinase) (mCERK) NEUROD1 2q32 neurogenic differentiation 1 SSFA2 2q32.1 sperm specific antigen 2 LOC344318 2q32.1 similar to Keratin, type I cytoskeletal 18 (Cytokeratin 18) (K18) (CK 18) LOC151242 2q32.1 protein phosphatase 1 regulatory subunit 1A PDE1A 2q32 phosphodiesterase 1A, calmodulin-dependent ERdj5 2q32.1 ER-resident protein ERdj5 FRZB 2q24-q31 frizzled-related protein NCKAP1 2q32 NCK-associated protein 1 LOC344320 2q32.1 similar to keratin 8, type II cytoskeletal - human DUSP19 2q32.1 dual specificity phosphatase 19 LOC129401 2q32.1 mitotic phosphoprotein 44 LOC129402 2q32.1 similar to lin-28 homolog; RNA-binding protein LIN-28; zinc finger, CCHC domain containing 1 LOC150503 2q32.1 similar to calcyclin binding protein LOC91752 2q32.1 similar to C630007C17Rik protein PRO2964 2q32.1 hypothetical protein PRO2964 LOC389066 2 LOC389066 LOC151273 2q32.1 similar to E74-like factor 2 (ets domain transcription factor); new Ets-related factor FLJ34780 2q32.1 hypothetical protein FLJ34780
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 2641 - 356 - 1999 10366743
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Hearing/Equilibriumearinnercochlea  
    Nervousbrain    
    Visualeye   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsensory   
    Nervouscentral   
    Nervousperipherous   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Endocrineislet cell (alpha,beta...)
    cell lineage expression profile that is restricted to progenitors/neuroblasts
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text brain, placenta (first trimester)
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • basic helix-loop-helix (HLH) protein
  • four E-boxes and two GC boxes in the transactivation domain, associating with the coactivator CREBBP and EP300
  • mono polymer heteromer , dimer
    HOMOLOGY
    interspecies ortholog to neurod, Danio rerio
    ortholog to Neurod1, ortholog to Neurod1, Rattus norvegicus
    ortholog to NEUROD1,
    Homologene
    FAMILY
  • NeurodD family of BHLH (basic helix loop helix) transcription factors
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm
    text retained in the cytoplasm of multiple endoccrine neoplasia type 1 islet and pancreatic endocrine tumor cells
    basic FUNCTION
  • critical for the normal development of several specialized cell types arising from the gut endoderm
  • regulating granule cell differentiation in the cerebellum and hippocampus
  • neurogenesis regulator D1 playing a role in neuronal differentiation
  • transactivating NEUROD2 in trophoblast cells (NEUROD differentiation cascade during first trimester human placental development)
  • proneural basic helix-loop-helix (bHLH) transcription factors not only initiating neuronal differentiation but also potentiating cell migration
  • important in the development of the hippocampal dentate gyrus and the cerebellum, and regulates neuronal and sensory cell development in both the cochlear and vestibular systems
  • a specific and an essential role of neuroD in photoreceptor formation in the chick retina
  • plays an important role in the development of the pancreas and the nervous system
  • contribute to both beta cell-specific and glucose-responsive insulin gene transcription
  • early function of NEUROD1 in regulating the specification of alpha, PP and epsilon cells
  • critical role of for NEUROG2 and NEUROD1 in controlling neuronal commitment and hippocampal granule neuroblast formation, both during embryonic development and in post-natal hippocampal granule neurogenesis
  • cell-intrinsically required for the survival and maturation of adult-born neurons
  • predominantly expressed in the nervous system late in development and is therefore more likely to be involved in terminal differentiation, neuronal maturation and survival
  • having functions cell intrinsically in progenitors/immature neurons to promote their survival and maturation into mature granule neurons
  • regulating expression of the insulin gene
  • differentiation factor required for dendrite morphogenesis and maintenance in the cerebellar cortex
  • a downstream effector of Wnts in adult neurogenesis selectively expressed in dividing neural progenitors and in immature granule neurons in the adult dentate gyrus
  • is both necessary and sufficient to induce key steps in terminal neuronal differentiation
  • critical for glucagon gene transcription and alpha cell differentiation
  • critical role of the neuronal differentiation factor NEUROD1 in neuroblastoma as well as its functional relationship with the neuronal repellent factor SLIT2
  • involved in the development of neural and endocrine structures, including the retina and pineal gland
  • is a lineage-dependent oncogene acting through its downstream target, NTRK2, across multiple cancer types
  • CELLULAR PROCESS cell life, differentiation
    nucleotide, transcription
    cell organization/biogenesis
    PHYSIOLOGICAL PROCESS development , nervous system
    text neurogenesis
    PATHWAY
    metabolism
    signaling sensory transduction/hearing
    a component
  • heterodimerizing with other bhlh proteins and activating transcription of gene that contain a specific DNA sequence known as the E-box
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • proopiomelanocortin, POMC
  • E1A binding protein p300, EP300
  • huntingtin-associated protein 1,HAP1 and mixed-lineage kinase 2, MLK2
  • ras responsive element binding protein 1, RREB1
  • v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (avian), MAFA
  • regulates insulin gene (INS) expression by binding to a critical E-box motif on the INS promoter
  • NKX2-2 in order to regulate pancreatic islet cell fates, and this epistatic relationship is cell-type dependen)
  • transcriptional activator for insulin gene expression, and the interactions of ISL1 with NEUROD1 are required for the transcriptional activity of the insulin gene
  • interacting with PAX6 (binds directly and activates the promoter region of MAFB, MAF, and NEUROD1 genes in pancreatic alpha cells)
  • ATF2 interacts with beta-cell-enriched transcription factors, MAFA, PDX1, and NEUROD1, and activates insulin gene transcription
  • INSM2 plays potentially an important role in the differentiation cascade of NEUROG3/NEUROD1 signaling in pancreatic islets
  • implicated in the neurogenesis and early differentiation of pancreatic endocrine cells
  • directly bound to the first and second E-box of the SLIT2 promoter region
  • essential for NHLH1 induction
  • upstream regulator of NHLH1 expression, but not NHLH2 expression
  • NEUROD4 and NEUROD6 are factors that are closely related to NEUROD1 and NEUROD2
  • downstream target of ATOH1, having potentially an independent role that is unrelated to the survival or differentiation of the inner ear hair cells
  • EYA1 and SIX1 are key transcription factors in initiating the neuronal developmental program, probably by recruiting and interacting with the SWI/SNF chromatin-remodeling complex to specifically mediate NEUROG1 and NEUROD1 transcription
  • may act through AIPL1 and other genes to maintain photoreceptor homeostasis
  • NKX2.2 represses NEUROD1 in pancreatic alpha cells
  • NTRK2 and NCAM1 are downstream targets of NEUROD1 that contribute to the actions of NEUROD1 in neuroendocrine lung
  • NEUROG2, NEUROD1, and EBF3 inducing MTURN
  • cell & other
    REGULATION
    activated by neurogenin 3 (NGN3) at early stage of islet cell differentiation
    MAP3K10 (facilitated by HD and HAP1)
    valproic acid, for the induction and suppression of neuronal and glial differentiation
    repressed by cyclin D1, CCND1
    Other phosphorylated in islet cells upon glucose stimulation
    in activated neurons, phosphorylation promotes dendritic growth
    ASSOCIATED DISORDERS
    corresponding disease(s) MODY6
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --other  
    differentially expressed in pituitary adenomas
    tumoral     --over  
    was closely associated with poor prognosis in neuroblastoma
    Susceptibility NIDDM18
    Variant & Polymorphism other
  • H241Q mutation seems to be associated with disease among set of MODYX families and to precipitate type 2-like diabetes in excessively obese individuals
  • Candidate gene
    Marker
  • NEUROD1 promoter methylation is a chemosensitivity marker in estrogen receptor-negative breast cancer
  • Therapy target
    ANIMAL & CELL MODELS
  • Mice carrying a targeted disruption of the BETA2 gene develop severe diabetes and die perinatally
  • mice homozygous for a targeted disruption of Neurod1 dislay abnormal pancreatic islet morphogenesis and develop diabetes due in part to inadequate expression of the insulin gene 2
  • Mice carrying a BETA2/NeuroD1 null mutation exhibit behavioral abnormalities suggestive of an inner ear defect, including lack of responsiveness to sound, hyperactivity, head tilting, and circling
  • mice with an inducible stem cell
  • specific deletion of Neurod1, resulting in substantially fewer newborn neurons in the hippocampus and olfactory bulb