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FLASH GENE
Symbol NEUROG3 contributors: mct/npt/pgu - updated : 17-10-2017
HGNC name neurogenin 3
HGNC id 13806
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