Description: Homo sapiens neuronal differentiation 1 (NEUROD1), mRNA. RefSeq Summary (NM_002500): This gene encodes a member of the NeuroD family of basic helix-loop-helix (bHLH) transcription factors. The protein forms heterodimers with other bHLH proteins and activates transcription of genes that contain a specific DNA sequence known as the E-box. It regulates expression of the insulin gene, and mutations in this gene result in type II diabetes mellitus. [provided by RefSeq, Jul 2008]. Transcript (Including UTRs) Position: hg19 chr2:182,540,833-182,545,392 Size: 4,560 Total Exon Count: 2 Strand: - Coding Region Position: hg19 chr2:182,542,517-182,543,587 Size: 1,071 Coding Exon Count: 1
ID:NDF1_HUMAN DESCRIPTION: RecName: Full=Neurogenic differentiation factor 1; Short=NeuroD; Short=NeuroD1; AltName: Full=Class A basic helix-loop-helix protein 3; Short=bHLHa3; FUNCTION: Acts as a transcriptional activator: mediates transcriptional activation by binding to E box-containing promoter consensus core sequences 5'-CANNTG-3'. Associates with the p300/CBP transcription coactivator complex to stimulate transcription of the secretin gene as well as the gene encoding the cyclin-dependent kinase inhibitor CDKN1A. Contributes to the regulation of several cell differentiation pathways, like those that promote the formation of early retinal ganglion cells, inner ear sensory neurons, granule cells forming either the cerebellum or the dentate gyrus cell layer of the hippocampus, endocrine islet cells of the pancreas and 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 and maintenance in the cerebellar cortex. Associates with chromatin to enhancer regulatory elements in genes encoding key transcriptional regulators of neurogenesis (By similarity). SUBUNIT: Interacts (via helix-loop-helix motif domain) with EP300 (via C-terminus) (By similarity). Heterodimer with TCF3/E47; the heterodimer is inhibited in presence of ID2, but not NR0B2, to E- box element. Efficient DNA-binding requires dimerization with another bHLH protein. Interacts with RREB1. Interacts with EP300; the interaction is inhibited by NR0B2. Interacts with TCF3; the interaction is inhibited by ID2. SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus. Note=In pancreatic islet cells, shuttles to the nucleus in response to glucose stimulation (By similarity). Colocalizes with NR0B2 in the nucleus. PTM: Phosphorylated. In islet cells, phosphorylated on Ser-274 upon glucose stimulation; which may be required for nuclear localization. In activated neurons, phosphorylated on Ser-335; which promotes dendritic growth. Phosphorylated by MAPK1; phosphorylation regulates heterodimerization and DNA-binding activities. Phosphorylation on Ser-266 and Ser-274 increases transactivation on the insulin promoter in glucose-stimulated insulinoma cells (By similarity). DISEASE: Defects in NEUROD1 are the cause of maturity-onset diabetes of the young type 6 (MODY6) [MIM:606394]. MODY is a form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease. SIMILARITY: Contains 1 bHLH (basic helix-loop-helix) domain. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/NEUROD1";
beta-cell function; diabetes, type 1 Mochizuki, M. et al. 2002, The association of Ala45Thr polymorphism in NeuroD with child-onset Type 1a diabetes in Japanese., Diabetes research and clinical practice. 2002 Jan;55(1):7-Nov.
[PubMed 11755474]
In conclusion, the Ala45Thr polymorphism contributes to the risk of development of, and to the early deterioration of beta-cell function, in Type 1a diabetes among the Japanese population.
Cardiovascular Diseases Martin G Larson et al. BMC medical genetics 2007, Framingham Heart Study 100K project: genome-wide associations for cardiovascular disease outcomes., BMC medical genetics.
[PubMed 17903304]
No association attained genome-wide significance, but several intriguing findings emerged. Notably, we replicated associations of chromosome 9p21 with major CVD. Additional studies are needed to validate these results. Finding genetic variants associated with CVD may point to novel disease pathways and identify potential targeted preventive therapies.
diabetes, type 1 Cinek, O. et al. 2003, NEUROD polymorphism Ala45Thr is associated with Type 1 diabetes mellitus in Czech children., Diabetes research and clinical practice. 2003 Apr;60(1):49-56.
[PubMed 12639765]
Our results confirm that the NEUROD Ala45Thr polymorphism is associated with childhood-onset Type 1 DM.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q13562
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0001102 RNA polymerase II activating transcription factor binding GO:0001105 RNA polymerase II transcription coactivator activity GO:0003677 DNA binding GO:0003682 chromatin binding GO:0003690 double-stranded DNA binding GO:0003700 transcription factor activity, sequence-specific DNA binding GO:0003713 transcription coactivator activity GO:0005515 protein binding GO:0008134 transcription factor binding GO:0043565 sequence-specific DNA binding GO:0046982 protein heterodimerization activity GO:0046983 protein dimerization activity GO:0070888 E-box binding
Biological Process: GO:0003326 pancreatic A cell fate commitment GO:0003329 pancreatic PP cell fate commitment GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006366 transcription from RNA polymerase II promoter GO:0006913 nucleocytoplasmic transport GO:0007263 nitric oxide mediated signal transduction GO:0007275 multicellular organism development GO:0007399 nervous system development GO:0009749 response to glucose GO:0009952 anterior/posterior pattern specification GO:0021542 dentate gyrus development GO:0021549 cerebellum development GO:0022008 neurogenesis GO:0023019 signal transduction involved in regulation of gene expression GO:0030073 insulin secretion GO:0030154 cell differentiation GO:0030902 hindbrain development GO:0031018 endocrine pancreas development GO:0035881 amacrine cell differentiation GO:0035883 enteroendocrine cell differentiation GO:0042493 response to drug GO:0042593 glucose homeostasis GO:0043010 camera-type eye development GO:0043065 positive regulation of apoptotic process GO:0045165 cell fate commitment GO:0045597 positive regulation of cell differentiation GO:0045664 regulation of neuron differentiation GO:0045666 positive regulation of neuron differentiation GO:0045893 positive regulation of transcription, DNA-templated GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0046426 negative regulation of JAK-STAT cascade GO:0048562 embryonic organ morphogenesis GO:0048666 neuron development GO:0048839 inner ear development GO:0050796 regulation of insulin secretion GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity GO:0060730 regulation of intestinal epithelial structure maintenance GO:0071156 regulation of cell cycle arrest GO:0071333 cellular response to glucose stimulus GO:2000675 negative regulation of type B pancreatic cell apoptotic process GO:2000679 positive regulation of transcription regulatory region DNA binding
HQ426678 - Homo sapiens clone 22 ceramide kinase-like isoform 8 mRNA, complete cds. JF290420 - Homo sapiens ceramide kinase-like protein isoform 8 mRNA, complete cds. AJ697857 - Homo sapiens partial mRNA for ceramide kinase-like protein (CERKL gene), variant 3. AB593070 - Homo sapiens NEUROD1 mRNA for neurogenic differentiation factor 1, complete cds, clone: HP05315-RBd13F05. AB593068 - Homo sapiens NEUROD1 mRNA for neurogenic differentiation factor 1, complete cds, clone: HP05315-RBb12B09. AB593071 - Homo sapiens NEUROD1 mRNA for neurogenic differentiation factor 1, complete cds, clone: HP05315-RBd77G05. AB593069 - Homo sapiens NEUROD1 mRNA for neurogenic differentiation factor 1, complete cds, clone: HP05315-RBb30G01. D82347 - Homo sapiens mRNA for NeuroD, complete cds. JD097069 - Sequence 78093 from Patent EP1572962. BC009046 - Homo sapiens neurogenic differentiation 1, mRNA (cDNA clone MGC:9038 IMAGE:3873419), complete cds. JD234317 - Sequence 215341 from Patent EP1572962. JD284458 - Sequence 265482 from Patent EP1572962. JD499130 - Sequence 480154 from Patent EP1572962. JB759088 - Sequence 13 from Patent WO2013102203. JD287393 - Sequence 268417 from Patent EP1572962. JD244098 - Sequence 225122 from Patent EP1572962. JD268741 - Sequence 249765 from Patent EP1572962. JD233742 - Sequence 214766 from Patent EP1572962. BT019731 - Homo sapiens neurogenic differentiation 1 mRNA, complete cds. DQ891560 - Synthetic construct clone IMAGE:100004190; FLH178062.01X; RZPDo839G12126D neurogenic differentiation 1 (NEUROD1) gene, encodes complete protein. AK313799 - Homo sapiens cDNA, FLJ94416, highly similar to Homo sapiens neurogenic differentiation 1 (NEUROD1), mRNA. KJ891691 - Synthetic construct Homo sapiens clone ccsbBroadEn_01085 NEUROD1 gene, encodes complete protein. KR709663 - Synthetic construct Homo sapiens clone CCSBHm_00004997 NEUROD1 (NEUROD1) mRNA, encodes complete protein. KR709664 - Synthetic construct Homo sapiens clone CCSBHm_00004998 NEUROD1 (NEUROD1) mRNA, encodes complete protein. KR709665 - Synthetic construct Homo sapiens clone CCSBHm_00005000 NEUROD1 (NEUROD1) mRNA, encodes complete protein. KR709666 - Synthetic construct Homo sapiens clone CCSBHm_00005002 NEUROD1 (NEUROD1) mRNA, encodes complete protein. DQ894747 - Synthetic construct Homo sapiens clone IMAGE:100009207; FLH178058.01L; RZPDo839G12125D neurogenic differentiation 1 (NEUROD1) gene, encodes complete protein. KU178230 - Homo sapiens neurogenic differentiation 1 isoform 1 (NEUROD1) mRNA, partial cds. KU178231 - Homo sapiens neurogenic differentiation 1 isoform 2 (NEUROD1) mRNA, complete cds, alternatively spliced. AB385071 - Synthetic construct DNA, clone: pF1KB5244, Homo sapiens NEUROD1 gene for neurogenic differentiation factor 1, complete cds, without stop codon, in Flexi system. CU679237 - Synthetic construct Homo sapiens gateway clone IMAGE:100017085 5' read NEUROD1 mRNA. GQ904713 - Homo sapiens neurogenic differentiation factor 1 (NEUROD1) mRNA, partial cds. U80578 - Human basic helix-loop-helix transcription factor (NeuroD) mRNA, partial cds. U36472 - Human putative neuroD homolog mRNA, partial cds. U50823 - Human neurod mRNA, partial cds. JD394719 - Sequence 375743 from Patent EP1572962.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa04950 - Maturity onset diabetes of the young
Reactome (by CSHL, EBI, and GO)
Protein Q13562 (Reactome details) participates in the following event(s):
R-HSA-210746 Regulation of gene expression in endocrine-committed (NEUROG3+) progenitor cells R-HSA-186712 Regulation of beta-cell development R-HSA-1266738 Developmental Biology
GeneReviews article(s) related to gene NEUROD1: mody-ov (Maturity-Onset Diabetes of the Young Overview) rp-overview (Nonsyndromic Retinitis Pigmentosa Overview)
Gene Model Information
category:
coding
nonsense-mediated-decay:
no
RNA accession:
NM_002500.4
exon count:
2
CDS single in 3' UTR:
no
RNA size:
3002
ORF size:
1071
CDS single in intron:
no
Alignment % ID:
99.97
txCdsPredict score:
2312.00
frame shift in genome:
no
% Coverage:
100.00
has start codon:
yes
stop codon in genome:
no
# of Alignments:
1
has end codon:
yes
retained intron:
no
# AT/AC introns
0
selenocysteine:
no
end bleed into intron:
0
# strange splices:
0
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Methods, Credits, and Use Restrictions
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for details on how this gene model was made and data restrictions if any.
US Server
