neurogenic differentiation factor 1; neuroD; neuroD1; class A basic helix-loop-helix protein 3; bHLHa3 (NEUROD1, BHLHA3, NEUROD)

Function

• acts as a transcriptional activator
• mediates transcriptional activation by binding to E box- containing promoter consensus core sequences 5'-CANNTG-3'
• associates with p300/CBP transcription coactivator complex to stimulate transcription of the secretin gene as well as the gene for the CDK inhibitor CDKN1A
• regulation of several cell differentiation pathways, such as those that promote formation of
  • early retinal ganglion cells
  • inner ear sensory neurons
  • granule cells forming the cerebellum
  • granule cells forming the dentate gyrus cell layer of the hippocampus
  • endocrine islet cells of the pancreas
  • enteroendocrine cells of the small intestine
• together with PAX6 or SIX3, is required for the regulation of amacrine cell fate specification
• also required for dendrite morphogenesis & maintenance in the cerebellar cortex
• associates with chromatin to enhancer regulatory elements in genes encoding key transcriptional regulators of neurogenesis
• phosphorylated
• in islet cells, phosphorylation on Ser-274 upon glucose stimulation may be required for nuclear localization
• in activated neurons, phosphorylation on Ser-335 promotes dendritic growth
• phosphorylation by MAPK1 regulates heterodimerization & DNA-binding activities
• phosphorylation on Ser-266 & Ser-274 increases transactivation on the insulin promoter in glucose-stimulated insulinoma cells (putative)
• interacts (via helix-loop-helix motif domain) with EP300 (via C-terminus) (putative)
• heterodimer with TCF3/E47
  • binding to the E-box element is inhibited by ID2
• efficient DNA-binding requires dimerization with another bHLH protein
• interacts with RREB1
• interacts with EP300: interaction is inhibited by NR0B2
• interacts with TCF3: interaction is inhibited by ID2

Structure

• contains 1 basic helix-loop-helix (bHLH) domain

Compartment

• cytoplasm (putative)
• nucleus
• in pancreatic islet cells, shuttles to the nucleus in response to glucose stimulation (putative)
• colocalizes with NR0B2 in the nucleus

Pathology

• defects in NEUROD1 are the cause of maturity-onset diabetes of the young type 6

More general terms

• neurogenic differentiation factor
• phosphoprotein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=4760
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:4760
• OMIM: https://mirror.omim.org/entry/125853
• OMIM: https://mirror.omim.org/entry/601724
• OMIM: https://mirror.omim.org/entry/606391
• OMIM: https://mirror.omim.org/entry/606394
• UniProt: http://www.uniprot.org/uniprot/Q13562.html