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FLASH GENE
Symbol NEUROG3 contributors: mct/npt/pgu - updated : 17-10-2017
HGNC name neurogenin 3
HGNC id 13806
Corresponding disease
DIAR4 congenital malabsorptive diarrhea 4
Location 10q22.1      Physical location : 71.331.791 - 71.333.210
Synonym name
  • protein atonal homolog 5
  • class A basic helix-loop-helix protein 7
  • Synonym symbol(s) NGN3, ATOH5, MATH4B, bHLHa7
    DNA
    TYPE functioning gene
    STRUCTURE 2.01 kb     2 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    CARP-1 10q22.1 cell-cycle and apoptosis regulatory protein 1 C10orf24 10q22.1 chromosome 10 open reading frame 24 DDX50 10q22.1 DEAD (Asp-Glu-Ala-Asp) box polypeptide 50 DDX21 10q21 DEAD (Asp-Glu-Ala-Asp) box polypeptide 21 KIAA1279 10q22.1 KIAA1279 LOC389976 10 similar to actin 3 - fruit fly (Drosophila melanogaster) (fragments) PRG1 10q22.1 proteoglycan 1, secretory granule VPS26 10q21.1 vacuolar protein sorting 26 (yeast) SUPV3L1 10q22.1 suppressor of var1, 3-like 1 (S. cerevisiae) FLJ22761 10q22.1 hypothetical protein FLJ22761 HK1 10q22 hexokinase 1 TACR2 10q22.1 tachykinin receptor 2 NET-7 10q22.1 transmembrane 4 superfamily member tetraspan NET-7 NEUROG3 10q21.3 neurogenin 3 C10orf35 10q22.2 chromosome 10 open reading frame 35 LOC389977 10 similar to ribosomal protein L5; 60S ribosomal protein L5 COL13A1 10q21.2-q22.1 collagen, type XIII, alpha 1 LOC387686 10 LOC387686 H2AFY2 10q22.3 H2A histone family, member Y2 AMID 10q22.2 apoptosis-inducing factor (AIF)-homologous mitochondrion-associated inducer of death MGC34695 10q22.2 hypothetical protein MGC34695 SARA1 10q22.2 SAR1a gene homolog 1 (S. cerevisiae) CALM2P2 10q22.2 calmodulin 2 pseudogene 2 PP 10q22.1-q22.2 pyrophosphatase (inorganic) OT7T022 10q21-q22 neuropeptide FF 1; RFamide-related peptide receptor
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 1167 - 214 - 2000 10677506
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinerectum highly
     pancreas exocrine     Homo sapiens
    Endocrinepancreasislet of Langerhans    Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandularendocrine 
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Endocrineislet cell (alpha,beta...) Homo sapiens
    cell lineage endocrine progenitor cells
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    Text pancreas
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    basic helix-loop-helix (HLH) DNA binding domain
    HOMOLOGY
    interspecies homolog to Atoh5 murine atonal homolog 5
    intraspecies homolog to NEUROG1
    Homologene
    FAMILY BHLH transcription factor family
    CATEGORY DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    text
  • NEUROG3 and CCAR1 are co-localized in the nucleus
  • transiently exported from the cell nucleus to the cytoplasm when neuronal polarity is initiated, suggesting that the nucleo-cytoplasmic transport of the protein is important for its action on neuronal development
  • basic FUNCTION
  • determination of neural precursor cells in the neuroectoderm and specification of a common precursor for the four pancratic endocrine cell types
  • required for endocrine-cell development in the pancreas and intestine
  • transiently marks the progenitor cells that will become islet cells and initiates endocrine differentiation during embryonic development, regeneration, and transdifferentiation
  • during embryonic development, initiates the differentiation of the beta-cells and other islet cell types from pancreatic endoderm
  • crucial role in regulating the cell cycle during the differentiation of pancreatic islet cells
  • necessary and sufficient to promote cellular quiescence in pancreatic progenitors
  • inhibits proliferation in endocrine progenitors by inducing CDKN1A
  • potentially playing a central role in the generation of neuronal populations controlling energy homeostasis
  • MAFA, PDX1 and NEUROG3 (an upstream regulator of Beta2/NEUROD1) leads to the effective reprogramming of acinar cells into insulin-producing beta cells
  • the role that NEUROG3 plays during pancreas development is unique
  • functions as a master regulator of endocrine pancreas formation, and its deficiency leads to the development of diabetes
  • PDX1, NEUROG3 and MAFA, are very important in pancreatic development
  • restricts serotonergic neuron differentiation to the hindbrain
  • is necessary and sufficient for endocrine differentiation during pancreatic development and is expressed by a population of progenitor cells that give rise exclusively to hormone-secreting cells within islets
  • progenitor cell-cycle G1 lengthening, through its actions on stabilization of NEUROG3, is an essential variable in normal endocrine cell genesis
  • plays a critical role in pancreatic endocrine cell differentiation
  • CELLULAR PROCESS cell cycle
    nucleotide, transcription
    PHYSIOLOGICAL PROCESS development
    text
  • neuroectoderm
  • central nervous system development
  • PATHWAY
    metabolism
    signaling
    a component efficient DNA binding requires dimerization with another BHLH protein
    INTERACTION
    DNA DNA binding
    RNA
    small molecule
    protein
  • targeting MYT1, NHLH1, EBF3, EBF2, HES6, CBFA2T2, NEUROD1, NEUROD4 (bind these enhancers to activate targets that execute core programs regulating neurogenesis)
  • interacting with OVOL1
  • ONECUT1 in developing pancreas, directly activates the pro-endocrine transcription factor, NEUROG3
  • interacting with CDKN1A (CDKN1A plays an essential role in promoting cell cycle exit in endocrine progenitors downstream of NEUROG3)
  • INSM2 plays potentially an important role in the differentiation cascade of NEUROG3/NEUROD1 signaling in pancreatic islets
  • CCAR1 is a transcriptional coactivator for nuclear receptors, also interacting with NEUROG3
  • directly activates the expression of NEUROD1, which is also required for proper endocrine differentiation
  • GLIS3 regulates NEUROG3 through its distal promoter region
  • FOXA2 colocalizes with NEUROG3 in pancreatic progenitors, thus indicating a primary role for this factor in regulating NEUROG3 expression
  • PAK3 is a novel effector of NEUROG3 endocrinogenic function, known to control neuronal differentiation and implicated in X-linked intellectual disability
  • PDX1 activates downstream transcription factors NEUROG3 and PAX6, and may be one of the mechanisms that promote differentiation of induced pluripotent stem cells (iPSCs) into islet beta cells
  • cell & other
    REGULATION
    Phosphorylated by phosphorylation is driven by the actions of cyclin-dependent kinases 2 and 4/6 at G1/S cell-cycle checkpoint
    Other activation of STAT3 regulates the expression of NEUROG3 to subsequently drive differentiation of spermatogonial stem cells and progenitor spermatogonia in the mammalian germline
    multi-site phosphorylation of NEUROG3 controls its ability to promote pancreatic endocrine differentiation and to maintain beta cell function in the presence of pro-proliferation cues
    ASSOCIATED DISORDERS
    corresponding disease(s) DIAR4
    Susceptibility to type 2 diabetes
    Variant & Polymorphism SNP associated with hyperproinsulinaemia and progression toward type 2 diabetes
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS