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Q64289 (NDF1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified May 14, 2014. Version 108. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Neurogenic differentiation factor 1

Short name=NeuroD1
Alternative name(s):
Basic helix-loop-helix factor 1
Short name=BHF-1
Gene names
Name:Neurod1
Synonyms:Neurod
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length357 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.7

Subunit structure

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

Subcellular location

Cytoplasm. Nucleus. Note: Colocalizes with NR0B2 in the nucleus By similarity. In pancreatic islet cells, shuttles to the nucleus in response to glucose stimulation. Ref.6

Induction

Up-regulated by fentanyl. Down-regulated by miR-190. Ref.8

Post-translational modification

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. Phosphorylated. In islet cells, phosphorylated on Ser-274 upon glucose stimulation; which may be required for nuclear localization. In activated neurons, phosphorylated on Ser-336 by CaMK2; which promotes dendritic growth. Ref.6 Ref.7

Sequence similarities

Contains 1 bHLH (basic helix-loop-helix) domain.

Ontologies

Keywords
   Biological processDifferentiation
Neurogenesis
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   LigandDNA-binding
   Molecular functionActivator
Developmental protein
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processamacrine cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

anterior/posterior pattern specification

Inferred from electronic annotation. Source: Ensembl

cellular response to glucose stimulus

Inferred from direct assay Ref.6. Source: UniProtKB

cerebellum development

Inferred from expression pattern PubMed 12242038. Source: RGD

dentate gyrus development

Inferred from sequence or structural similarity. Source: UniProtKB

embryonic organ morphogenesis

Inferred from electronic annotation. Source: Ensembl

endocrine pancreas development

Inferred from sequence or structural similarity. Source: UniProtKB

enteroendocrine cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

inner ear development

Inferred from sequence or structural similarity. Source: UniProtKB

insulin secretion

Inferred from electronic annotation. Source: Ensembl

negative regulation of JAK-STAT cascade

Inferred from electronic annotation. Source: Ensembl

negative regulation of type B pancreatic cell apoptotic process

Inferred from electronic annotation. Source: Ensembl

nitric oxide mediated signal transduction

Inferred from electronic annotation. Source: Ensembl

nucleocytoplasmic transport

Inferred from direct assay Ref.6. Source: UniProtKB

pancreatic A cell fate commitment

Inferred from electronic annotation. Source: Ensembl

pancreatic PP cell fate commitment

Inferred from electronic annotation. Source: Ensembl

positive regulation of apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of neuron differentiation

Inferred from direct assay Ref.2. Source: RGD

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.6. Source: UniProtKB

positive regulation of transcription regulatory region DNA binding

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of cell cycle arrest

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of intestinal epithelial structure maintenance

Inferred from sequence or structural similarity. Source: UniProtKB

response to drug

Inferred from expression pattern PubMed 16635253. Source: RGD

signal transduction involved in regulation of gene expression

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from direct assay Ref.6. Source: UniProtKB

nucleus

Inferred from direct assay Ref.6. Source: UniProtKB

   Molecular_functionE-box binding

Inferred from electronic annotation. Source: Ensembl

RNA polymerase II transcription coactivator activity

Inferred from electronic annotation. Source: Ensembl

chromatin binding

Inferred from sequence or structural similarity. Source: UniProtKB

double-stranded DNA binding

Inferred from direct assay Ref.2. Source: RGD

sequence-specific DNA binding

Inferred from electronic annotation. Source: Ensembl

sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 357357Neurogenic differentiation factor 1
PRO_0000127384

Regions

Domain101 – 15353bHLH
Motif87 – 937Nuclear localization signal Potential
Compositional bias58 – 7720Glu-rich (acidic)
Compositional bias67 – 7610Poly-Glu
Compositional bias87 – 904Poly-Lys

Amino acid modifications

Modified residue1621Phosphoserine By similarity
Modified residue2591Phosphoserine By similarity
Modified residue2661Phosphoserine By similarity
Modified residue2741Phosphoserine Probable
Modified residue3361Phosphoserine; by CaMK2 Ref.7

Experimental info

Mutagenesis2591S → A: No effect on subcellular location. Ref.6
Mutagenesis2621T → A: No effect on subcellular location. Ref.6
Mutagenesis2661S → A: No effect on subcellular location. Ref.6
Mutagenesis2741S → A: Impairs translocation from the cytoplasm to the nucleus upon glucose stimulation. Ref.6
Mutagenesis2741S → D: No effect on subcellular location. Ref.6

Sequences

Sequence LengthMass (Da)Tools
Q64289 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: F773637E64D3E99E

FASTA35740,001
        10         20         30         40         50         60 
MTKSYSESGL MGEPQPQGPP SWTDECLSSQ DEEHEADKKE DELEAMNAEE DSLRNGGEEE 

        70         80         90        100        110        120 
DEDEDLEEEE EEEEEEDDQK PKRRGPKKKK MTKARLERFK LRRMKANARE RNRMHGLNAA 

       130        140        150        160        170        180 
LDNLRKVVPC YSKTQKLSKI ETLRLAKNYI WALSEILRSG KSPDLVSFVQ TLCKGLSQPT 

       190        200        210        220        230        240 
TNLVAGCLQL NPRTFLPEQN PDMPPHLPTA SASFPVHPYS YQSPGLPSPP YGTMDSSHVF 

       250        260        270        280        290        300 
HVKPPPHAYS AALEPFFESP LTDCTSPSFD GPLSPPLSIN GNFSFKHEPS TEFEKNYAFT 

       310        320        330        340        350 
MHYPAATLAG PQSHGSIFSS GAAAPRCEIP IDNIMSFDSH SHHERVMSAQ LNAIFHD 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and expression of a rat brain basic helix-loop-helix factor."
Kawakami H., Maruyama H., Yasunami M., Ohkubo H., Hara H., Saida T., Nakanishi S., Nakamura S.
Biochem. Biophys. Res. Commun. 221:199-204(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Cerebellum.
[2]"Overexpression of NeuroD in PC12 cells alters morphology and enhances expression of the adenylate kinase isozyme 1 gene."
Noma T., Yoon Y.S., Nakazawa A.
Brain Res. Mol. Brain Res. 67:53-63(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[3]"Cloning of rat NeuroD/Beta2."
Andersen F.G., Madsen O.D., Serup P.
Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: New England Deaconess Hospital.
Tissue: Pancreatic islet.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[5]"Developmental expression of neurogenic gene, NeuroD in the mammalian retina."
Ahmad I., Acharay H.R.
Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 88-200.
Strain: Sprague-Dawley.
Tissue: Retina.
[6]"Glucose induced MAPK signalling influences NeuroD1-mediated activation and nuclear localization."
Petersen H.V., Jensen J.N., Stein R., Serup P.
FEBS Lett. 528:241-245(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF SER-259; THR-262; SER-266 AND SER-274, PHOSPHORYLATION AT SER-274.
[7]"A CaMKII-NeuroD signaling pathway specifies dendritic morphogenesis."
Gaudilliere B., Konishi Y., de la Iglesia N., Yao G., Bonni A.
Neuron 41:229-241(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION AT SER-336.
[8]"Modulations of NeuroD activity contribute to the differential effects of morphine and fentanyl on dendritic spine stability."
Zheng H., Zeng Y., Chu J., Kam A.Y., Loh H.H., Law P.Y.
J. Neurosci. 30:8102-8110(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D82075 mRNA. Translation: BAA11536.1.
D82074 mRNA. Translation: BAA11535.1.
D82945 mRNA. Translation: BAA81821.1.
AF107728 mRNA. Translation: AAD19609.1.
BC092367 mRNA. Translation: AAH92367.1.
BC094526 mRNA. Translation: AAH94526.1.
U80603 mRNA. Translation: AAB38744.1.
PIRJC4703.
RefSeqNP_062091.1. NM_019218.2.
UniGeneRn.44289.

3D structure databases

ProteinModelPortalQ64289.
ModBaseSearch...
MobiDBSearch...

PTM databases

PhosphoSiteQ64289.

Proteomic databases

PaxDbQ64289.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000007662; ENSRNOP00000007662; ENSRNOG00000005609.
GeneID29458.
KEGGrno:29458.
UCSCRGD:3165. rat.

Organism-specific databases

CTD4760.
RGD3165. Neurod1.

Phylogenomic databases

eggNOGNOG287211.
GeneTreeENSGT00680000099860.
HOGENOMHOG000049256.
HOVERGENHBG000250.
InParanoidQ64289.
KOK08033.
OMAMNAQLNA.
OrthoDBEOG722J8S.
PhylomeDBQ64289.
TreeFamTF315153.

Gene expression databases

GenevestigatorQ64289.

Family and domain databases

Gene3D4.10.280.10. 1 hit.
InterProIPR011598. bHLH_dom.
IPR022575. Neurogenic_DUF.
IPR016637. TF_bHLH_NeuroD.
[Graphical view]
PfamPF00010. HLH. 1 hit.
PF12533. Neuro_bHLH. 1 hit.
[Graphical view]
PIRSFPIRSF015618. bHLH_NeuroD. 1 hit.
SMARTSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMSSF47459. SSF47459. 1 hit.
PROSITEPS50888. BHLH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio609242.
PROQ64289.

Entry information

Entry nameNDF1_RAT
AccessionPrimary (citable) accession number: Q64289
Secondary accession number(s): Q569P0
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: May 14, 2014
This is version 108 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families