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Protein

Neurogenic differentiation factor 1

Gene

Neurod1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.15 Publications

GO - Molecular functioni

GO - Biological processi

  • amacrine cell differentiation Source: UniProtKB
  • anterior/posterior pattern specification Source: MGI
  • camera-type eye development Source: MGI
  • cell fate commitment Source: MGI
  • cellular response to glucose stimulus Source: Ensembl
  • cerebellum development Source: UniProtKB
  • dentate gyrus development Source: UniProtKB
  • embryonic organ morphogenesis Source: BHF-UCL
  • endocrine pancreas development Source: UniProtKB
  • enteroendocrine cell differentiation Source: UniProtKB
  • glucose homeostasis Source: BHF-UCL
  • hindbrain development Source: MGI
  • inner ear development Source: UniProtKB
  • insulin secretion Source: MGI
  • negative regulation of JAK-STAT cascade Source: MGI
  • negative regulation of type B pancreatic cell apoptotic process Source: BHF-UCL
  • neuron development Source: InterPro
  • nitric oxide mediated signal transduction Source: MGI
  • nucleocytoplasmic transport Source: Ensembl
  • pancreatic A cell fate commitment Source: MGI
  • pancreatic PP cell fate commitment Source: MGI
  • positive regulation of apoptotic process Source: UniProtKB
  • positive regulation of cell differentiation Source: UniProtKB
  • positive regulation of neuron differentiation Source: UniProtKB
  • positive regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • positive regulation of transcription regulatory region DNA binding Source: MGI
  • regulation of cell cycle arrest Source: UniProtKB
  • regulation of intestinal epithelial structure maintenance Source: UniProtKB
  • regulation of neuron differentiation Source: MGI
  • response to drug Source: Ensembl
  • response to glucose Source: MGI
  • signal transduction involved in regulation of gene expression Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Activator, Developmental protein

Keywords - Biological processi

Differentiation, Neurogenesis, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiR-MMU-210745. Regulation of gene expression in beta cells.
R-MMU-210746. Regulation of gene expression in endocrine-committed (NEUROG3+) progenitor cells.

Names & Taxonomyi

Protein namesi
Recommended name:
Neurogenic differentiation factor 1
Short name:
NeuroD1
Alternative name(s):
Beta-cell E-box transcriptional activator 2
Short name:
Beta2
Gene namesi
Name:Neurod1
Synonyms:Neurod
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:1339708. Neurod1.

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus PROSITE-ProRule annotation

  • Note: In pancreatic islet cells, shuttles to the nucleus in response to glucose stimulation. Colocalizes with NR0B2 in the nucleus (By similarity).By similarity

GO - Cellular componenti

  • cytoplasm Source: MGI
  • intracellular Source: MGI
  • nucleoplasm Source: Reactome
  • nucleus Source: MGI
  • RNA polymerase II transcription factor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice are deaf and die shortly after birth due to neonatal diabetes that results from developmental and functional defects of the pancreatic endocrine cells. Show a loss of enteroendocrine cells in the small intestine, airway and alveolar epithelial cells in the lung, granular neuronal cells in the cerebellum, hippocampal dentate gyrus and sensory neurons in the inner ear due to extensive cell death that occurs during the early stages of differentiation.5 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi162S → A: Reduces weakly phosphorylation. Reduces strongly phosphorylation; when associated with A-259 and A-266. 1 Publication1
Mutagenesisi259S → A: Reduces weakly phosphorylation. Reduces strongly phosphorylation; when associated with A-162 and A-266. Reduces transactivation on the insulin promoter in glucose-stimulated insulinoma cells; when associated with A-266 and A-274. 2 Publications1
Mutagenesisi266S → A: Reduces weakly phosphorylation. Reduces strongly phosphorylation; when associated with A-162 and A-259. Reduces transactivation on the insulin promoter in glucose-stimulated insulinoma cells; when associated with A-259 and A-274. 2 Publications1
Mutagenesisi274S → A: Reduces strongly phosphorylation. Reduces transactivation on the insulin promoter in glucose-stimulated insulinoma cells; when associated with A-259 and A-266. 2 Publications1
Mutagenesisi279I → V: Promotes the formation of differentiated late retinal amacrine cells. 1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001273831 – 357Neurogenic differentiation factor 1Add BLAST357

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei162Phosphoserine1 Publication1
Modified residuei259Phosphoserine2 Publications1
Modified residuei266Phosphoserine2 Publications1
Modified residuei274Phosphoserine2 Publications1
Modified residuei336Phosphoserine; by CaMK2By similarity1

Post-translational modificationi

In islet cells, phosphorylated on Ser-274 upon glucose stimulation; which may be required for nuclear localization. In activated neurons, phosphorylated on Ser-336; which promotes dendritic growth (By similarity). 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 similarity2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ60867.
PaxDbiQ60867.
PRIDEiQ60867.

PTM databases

iPTMnetiQ60867.
PhosphoSitePlusiQ60867.

Expressioni

Tissue specificityi

Expressed in pancreatic beta cells, pulmonary neuroendocrine cells and retinal interneurons amacrine cells (at protein level). Expressed in endocrine cells of the pancreas. Expressed in the inner layer of cerebellar external granular layer (EGL). Expressed in the Ammon's horn (AH), which includes the CA1-CA3 pyramidal layer and in granule cells of the dentate gyrus (DG). Expressed in photoreceptors of the outer nuclear layer (ONL), in a subset of cells in the lower half of the inner nuclear layer (INL), and in a subset of cells in the ganglion cell layer (GCL) of the retina. Expressed in cholinergic and AII amacrine cell types. Expressed in differentiating neurons of both the central and peripheral nervous systems.6 Publications

Developmental stagei

Expressed in glucagon- and ghrelin-producing cells of the pancreas at 14.5 dpc. Expressed in each of the hormone-producing cells population of the pancreas, except somatostatin-producing cells at 16.5 dpc (at protein level). Expressed during embryonic development. Expressed in the earliest islet precursor cells of the pancreas at 9.5 dpc. Expressed in neuronal cells in the inner ear between 9.5 and 12.5 dpc. Expressed within the otic epithelium and among the delaminating cells migrating away from the ear to form sensory neurons at E10.5. Expressed in the upper blade of the nascent dentate gyrus at 16.5 dpc.5 Publications

Inductioni

Up-regulated by NKX2-2 and NEUROG3.2 Publications

Gene expression databases

BgeeiENSMUSG00000034701.
CleanExiMM_NEUROD1.
GenevisibleiQ60867. MM.

Interactioni

Subunit structurei

Heterodimer with TCF3/E47; the heterodimer is inhibited in presence of ID2, but not NR0B2, to E-box element. Interacts with EP300; the interaction is inhibited by NR0B2. Interacts with TCF3; the interaction is inhibited by ID2. Interacts with RREB1 (By similarity). Heterodimer with TCF3/E47. Efficient DNA-binding requires dimerization with another bHLH protein. Interacts (via helix-loop-helix motif domain) with EP300 (via C-terminus). Interacts with ATOH8.By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CCNDBP1O952734EBI-309315,EBI-748961From a different organism.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi201733. 10 interactors.
IntActiQ60867. 2 interactors.
MINTiMINT-8396397.
STRINGi10090.ENSMUSP00000040364.

Structurei

Secondary structure

1357
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi102 – 126Combined sources25
Beta strandi128 – 130Combined sources3
Beta strandi133 – 135Combined sources3
Helixi139 – 156Combined sources18

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2QL2X-ray2.50B/D102-160[»]
ProteinModelPortaliQ60867.
SMRiQ60867.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ60867.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini101 – 153bHLHPROSITE-ProRule annotationAdd BLAST53

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi87 – 93Nuclear localization signalSequence analysis7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi58 – 77Glu-rich (acidic)Add BLAST20
Compositional biasi58 – 64Poly-Glu7
Compositional biasi67 – 77Poly-GluAdd BLAST11
Compositional biasi87 – 90Poly-Lys4

Sequence similaritiesi

Contains 1 bHLH (basic helix-loop-helix) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410IQ4I. Eukaryota.
ENOG410Z6FG. LUCA.
GeneTreeiENSGT00680000099860.
HOGENOMiHOG000049256.
HOVERGENiHBG000250.
InParanoidiQ60867.
KOiK08033.
OMAiPDLMSFV.
OrthoDBiEOG091G15AI.
PhylomeDBiQ60867.
TreeFamiTF315153.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
IPR032652. Neurod1.
IPR022575. Neurogenic_DUF.
IPR016637. TF_bHLH_NeuroD.
[Graphical view]
PANTHERiPTHR19290:SF88. PTHR19290:SF88. 2 hits.
PfamiPF00010. HLH. 1 hit.
PF12533. Neuro_bHLH. 1 hit.
[Graphical view]
PIRSFiPIRSF015618. bHLH_NeuroD. 1 hit.
SMARTiSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiPS50888. BHLH. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q60867-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTKSYSESGL MGEPQPQGPP SWTDECLSSQ DEEHEADKKE DELEAMNAEE
60 70 80 90 100
DSLRNGGEEE EEDEDLEEEE EEEEEEEDQK PKRRGPKKKK MTKARLERFK
110 120 130 140 150
LRRMKANARE RNRMHGLNAA LDNLRKVVPC YSKTQKLSKI ETLRLAKNYI
160 170 180 190 200
WALSEILRSG KSPDLVSFVQ TLCKGLSQPT TNLVAGCLQL NPRTFLPEQN
210 220 230 240 250
PDMPPHLPTA SASFPVHPYS YQSPGLPSPP YGTMDSSHVF HVKPPPHAYS
260 270 280 290 300
AALEPFFESP LTDCTSPSFD GPLSPPLSIN GNFSFKHEPS AEFEKNYAFT
310 320 330 340 350
MHYPAATLAG PQSHGSIFSS GAAAPRCEIP IDNIMSFDSH SHHERVMSAQ

LNAIFHD
Length:357
Mass (Da):39,999
Last modified:February 1, 1997 - v2
Checksum:iB6626E1315E31027
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U28068 mRNA. Translation: AAC52203.1.
U28888 Genomic DNA. Translation: AAC52204.1.
AK005073 mRNA. Translation: BAB23797.1.
AK018781 mRNA. Translation: BAB31405.1.
BC018241 mRNA. Translation: AAH18241.1.
CCDSiCCDS16169.1.
PIRiI49338.
RefSeqiNP_035024.1. NM_010894.2.
UniGeneiMm.4636.

Genome annotation databases

EnsembliENSMUST00000041099; ENSMUSP00000040364; ENSMUSG00000034701.
GeneIDi18012.
KEGGimmu:18012.
UCSCiuc008kgt.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U28068 mRNA. Translation: AAC52203.1.
U28888 Genomic DNA. Translation: AAC52204.1.
AK005073 mRNA. Translation: BAB23797.1.
AK018781 mRNA. Translation: BAB31405.1.
BC018241 mRNA. Translation: AAH18241.1.
CCDSiCCDS16169.1.
PIRiI49338.
RefSeqiNP_035024.1. NM_010894.2.
UniGeneiMm.4636.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2QL2X-ray2.50B/D102-160[»]
ProteinModelPortaliQ60867.
SMRiQ60867.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201733. 10 interactors.
IntActiQ60867. 2 interactors.
MINTiMINT-8396397.
STRINGi10090.ENSMUSP00000040364.

PTM databases

iPTMnetiQ60867.
PhosphoSitePlusiQ60867.

Proteomic databases

MaxQBiQ60867.
PaxDbiQ60867.
PRIDEiQ60867.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000041099; ENSMUSP00000040364; ENSMUSG00000034701.
GeneIDi18012.
KEGGimmu:18012.
UCSCiuc008kgt.1. mouse.

Organism-specific databases

CTDi4760.
MGIiMGI:1339708. Neurod1.

Phylogenomic databases

eggNOGiENOG410IQ4I. Eukaryota.
ENOG410Z6FG. LUCA.
GeneTreeiENSGT00680000099860.
HOGENOMiHOG000049256.
HOVERGENiHBG000250.
InParanoidiQ60867.
KOiK08033.
OMAiPDLMSFV.
OrthoDBiEOG091G15AI.
PhylomeDBiQ60867.
TreeFamiTF315153.

Enzyme and pathway databases

ReactomeiR-MMU-210745. Regulation of gene expression in beta cells.
R-MMU-210746. Regulation of gene expression in endocrine-committed (NEUROG3+) progenitor cells.

Miscellaneous databases

EvolutionaryTraceiQ60867.
PROiQ60867.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000034701.
CleanExiMM_NEUROD1.
GenevisibleiQ60867. MM.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
IPR032652. Neurod1.
IPR022575. Neurogenic_DUF.
IPR016637. TF_bHLH_NeuroD.
[Graphical view]
PANTHERiPTHR19290:SF88. PTHR19290:SF88. 2 hits.
PfamiPF00010. HLH. 1 hit.
PF12533. Neuro_bHLH. 1 hit.
[Graphical view]
PIRSFiPIRSF015618. bHLH_NeuroD. 1 hit.
SMARTiSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiPS50888. BHLH. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNDF1_MOUSE
AccessioniPrimary (citable) accession number: Q60867
Secondary accession number(s): Q545N9, Q60897
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: February 1, 1997
Last modified: November 2, 2016
This is version 149 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.