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FLASH GENE

Symbol

NEUROG3

contributors: mct/npt/pgu - updated : 17-10-2017

HGNC name	neurogenin 3
HGNC id	13806

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_020999 2 - 1167 NP_066279 - 214 - 2000 10677506

EXPRESSION

Type	restricted

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 intestine large intestine rectum   highly   pancreas exocrine         Homo sapiens Endocrine pancreas islet of Langerhans       Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial secretory glandular endocrine

cells

System Cell Pubmed Species Stage Rna symbol Endocrine islet 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