Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q62414 (NDF2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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 2

Short name=NeuroD2
Alternative name(s):
NeuroD-related factor
Short name=NDRF
Gene names
Name:Neurod2
Synonyms:Ndrf
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length383 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transcriptional regulator implicated in neuronal determination. Mediates calcium-dependent transcription activation by binding to E box-containing promoter. Critical factor essential for the repression of the genetic program for neuronal differentiation; prevents the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons. Induces transcription of ZEB1, which in turn represses neuronal differentiation by down-regulating REST expression. Plays a role in the establishment and maturation of thalamocortical connections; involved in the segregation of thalamic afferents into distinct barrel domains within layer VI of the somatosensory cortex. Involved in the development of the cerebellar and hippocampal granular neurons, neurons in the basolateral nucleus of amygdala and the hypothalamic-pituitary axis. Associates with chromatin to the DPYSL3 E box-containing promoter. Ref.6 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14

Subunit structure

Interacts with TCF3, TCF4 and TCF12. Interacts with CDC20. Efficient DNA-binding and transcription activation require dimerization with another bHLH protein. Ref.12 Ref.13

Subcellular location

Nucleus Ref.6 Ref.11.

Tissue specificity

Expressed in the external germinal layer (EGL) and internal granular layer (IGL) of the cerebellum (at protein level). Expressed in layers V and VI of the neocortex at postnatal day 1. Expressed in all layers of the neocortex at postnatal day 4. Strongly expressed in layer IV of the neocortex, particularly in the barrel cortex at postnatal day 7. Expressed in the CA1, CA2 and CA3 and dentate gyrus of the hippocampus and many nuclei such as the habenular thalamic nuclei, paraventricular hypothalamic nuclei, amygdala nuclei, and pyramidal nucleus. Expressed in granule cells, molecular layer neurons, and deep cerebella nuclei of the cerebellum. Expressed in brainstem neurons in the external cuneate nucleus and central gray. Ref.8 Ref.10 Ref.14

Developmental stage

Expressed in dorsal and ventral parts of the lateral, basolateral and basomedial amygdala at 17 and 18 dpc (at protein level). Initially expressed in embryo at 11 dpc, with persistent expression in the nervous system until birth. Ref.9 Ref.12

Domain

The C-terminal region is necessary for depolarization-induced and calcium-dependent transcription activation.

Post-translational modification

Ubiquitinated by the APC/C complex; leading to its degradation in neurons. The CDC20-APC/C-induced degradation of NEUROD2 drives presynaptic differentiation. Ref.13

Disruption phenotype

Mice exhibit small brains, ataxia, reduced seizure threshold, growth failure, and postnatal premature death. Show excessive apoptosis in central nervous system. Lacks nuclei of the lateral and basolateral amygdala. Organization of cortical neurons into barrel structures is disrupted; thalamocortical axon terminals fail to segregate in the somatosensory cortex. Ref.7 Ref.8 Ref.9 Ref.10

Sequence similarities

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

Ontologies

Keywords
   Biological processDifferentiation
Neurogenesis
Transcription
Transcription regulation
   Cellular componentNucleus
   LigandDNA-binding
   Molecular functionActivator
Developmental protein
   PTMUbl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processassociative learning

Inferred from mutant phenotype Ref.9. Source: MGI

behavioral fear response

Inferred from mutant phenotype Ref.9. Source: MGI

cellular response to calcium ion

Inferred from direct assay Ref.10. Source: UniProtKB

cellular response to electrical stimulus

Inferred from direct assay Ref.10. Source: UniProtKB

cerebellar cortex development

Inferred from mutant phenotype Ref.10. Source: UniProtKB

negative regulation of synapse maturation

Inferred from direct assay Ref.13. Source: UniProtKB

neuron development

Inferred from mutant phenotype Ref.9. Source: MGI

positive regulation of calcium-mediated signaling

Inferred from direct assay Ref.10. Source: UniProtKB

positive regulation of neuron differentiation

Inferred from direct assay Ref.6Ref.11Ref.12Ref.14. Source: UniProtKB

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from direct assay Ref.8Ref.10. Source: UniProtKB

positive regulation of synapse maturation

Inferred from mutant phenotype Ref.10. Source: UniProtKB

positive regulation of synaptic plasticity

Inferred from direct assay Ref.13. Source: UniProtKB

protein ubiquitination

Inferred from direct assay Ref.13. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentnucleus

Inferred from direct assay Ref.6Ref.11Ref.14. Source: UniProtKB

   Molecular_functionDNA binding

Inferred from direct assay Ref.9. Source: MGI

E-box binding

Inferred from direct assay Ref.8Ref.12. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.12Ref.13. Source: UniProtKB

protein heterodimerization activity

Inferred from direct assay Ref.12. Source: UniProtKB

transcription corepressor activity

Inferred from direct assay Ref.14. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 383383Neurogenic differentiation factor 2
PRO_0000127388

Regions

Domain122 – 17453bHLH
Motif108 – 1147Nuclear localization signal Potential
Compositional bias83 – 9210Poly-Glu
Compositional bias283 – 2864Poly-Gly

Experimental info

Mutagenesis131 – 1322ER → AQ: Inhibits neurons differentiation. Ref.6
Sequence conflict411P → S in AAC26057. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q62414 [UniParc].

Last modified October 10, 2003. Version 3.
Checksum: 68342005219829B1

FASTA38341,493
        10         20         30         40         50         60 
MLTRLFSEPG LLSDVPKFAS WGDGDDDEPR SDKGDAPPQP PPAPGSGAPG PARAAKPVSL 

        70         80         90        100        110        120 
RGGEEIPEPT LAEVKEEGEL GGEEEEEEEE EEGLDEAEGE RPKKRGPKKR KMTKARLERS 

       130        140        150        160        170        180 
KLRRQKANAR ERNRMHDLNA ALDNLRKVVP CYSKTQKLSK IETLRLAKNY IWALSEILRS 

       190        200        210        220        230        240 
GKRPDLVSYV QTLCKGLSQP TTNLVAGCLQ LNSRNFLTEQ GADGAGRFHG SGGPFAMHPY 

       250        260        270        280        290        300 
PYPCSRLAGA QCQAAGGLGG GAAHALRTHG YCAAYETLYA AAGGGGASPD YNSSEYEGPL 

       310        320        330        340        350        360 
SPPLCLNGNF SLKQDSSPDH EKSYHYSMHY SALPGSRPTG HGLVFGSSAV RGGVHSENLL 

       370        380 
SYDMHLHHDR GPMYEELNAF FHN 

« Hide

References

« Hide 'large scale' references
[1]"NeuroD2 and neuroD3: distinct expression patterns and transcriptional activation potentials within the neuroD gene family."
McCormick M.B., Tamimi R.M., Snider L., Asakura A., Bergstrom D., Tapscott S.J.
Mol. Cell. Biol. 16:5792-5800(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]Tapscott S.J., McCormick M.B., Tamimi R.T.
Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION TO 338-339.
[3]"Molecular cloning and characterization of a cDNA encoding a novel basic helix-loop-helix protein structurally related to Neuro-D/BHF1."
Yasunami M., Suzuki K., Maruyama H., Kawakami H., Nagai Y., Hagiwara M., Ohkubo H.
Biochem. Biophys. Res. Commun. 220:754-758(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Embryo.
[4]"Structure of the mouse NDRF gene and its regulation during neuronal differentiation of P19 cells."
Oda H., Iwata I., Yasunami M., Ohkubo H.
Brain Res. Mol. Brain Res. 77:37-46(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: C57BL/6.
[5]"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].
Strain: C57BL/6.
Tissue: Brain.
[6]"Generation of neurons by transient expression of neural bHLH proteins in mammalian cells."
Farah M.H., Olson J.M., Sucic H.B., Hume R.I., Tapscott S.J., Turner D.L.
Development 127:693-702(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF 131-GLU-ARG-132, SUBCELLULAR LOCATION.
[7]"NeuroD2 is necessary for development and survival of central nervous system neurons."
Olson J.M., Asakura A., Snider L., Hawkes R., Strand A., Stoeck J., Hallahan A., Pritchard J., Tapscott S.J.
Dev. Biol. 234:174-187(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[8]"Regulation of neuroD2 expression in mouse brain."
Lin C.H., Stoeck J., Ravanpay A.C., Guillemot F., Tapscott S.J., Olson J.M.
Dev. Biol. 265:234-245(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DNA-BINDING, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
[9]"The dosage of the neuroD2 transcription factor regulates amygdala development and emotional learning."
Lin C.H., Hansen S., Wang Z., Storm D.R., Tapscott S.J., Olson J.M.
Proc. Natl. Acad. Sci. U.S.A. 102:14877-14882(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CHROMATIN-BINDING, DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE.
[10]"Regulation of thalamocortical patterning and synaptic maturation by NeuroD2."
Ince-Dunn G., Hall B.J., Hu S.C., Ripley B., Huganir R.L., Olson J.M., Tapscott S.J., Ghosh A.
Neuron 49:683-695(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.
[11]"Transduction of NeuroD2 protein induced neural cell differentiation."
Noda T., Kawamura R., Funabashi H., Mie M., Kobatake E.
J. Biotechnol. 126:230-236(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[12]"E protein dosage influences brain development more than family member identity."
Ravanpay A.C., Olson J.M.
J. Neurosci. Res. 86:1472-1481(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH TCF3; TCF4 AND TCF12, DNA-BINDING, DEVELOPMENTAL STAGE.
[13]"A Cdc20-APC ubiquitin signaling pathway regulates presynaptic differentiation."
Yang Y., Kim A.H., Yamada T., Wu B., Bilimoria P.M., Ikeuchi Y., de la Iglesia N., Shen J., Bonni A.
Science 326:575-578(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CDC20, UBIQUITINATION.
[14]"Transcriptional inhibition of REST by NeuroD2 during neuronal differentiation."
Ravanpay A.C., Hansen S.J., Olson J.M.
Mol. Cell. Neurosci. 44:178-189(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U58471 mRNA. Translation: AAC26057.1.
D83507 mRNA. Translation: BAA11931.1.
AB027126 Genomic DNA. Translation: BAA96490.1.
BC058965 mRNA. Translation: AAH58965.1.
CCDSCCDS25343.1.
PIRJC4688.
RefSeqNP_035025.3. NM_010895.3.
UniGeneMm.4814.

3D structure databases

ProteinModelPortalQ62414.
SMRQ62414. Positions 123-180.
ModBaseSearch...
MobiDBSearch...

PTM databases

PhosphoSiteQ62414.

Proteomic databases

MaxQBQ62414.
PaxDbQ62414.
PRIDEQ62414.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000041685; ENSMUSP00000041373; ENSMUSG00000038255.
GeneID18013.
KEGGmmu:18013.
UCSCuc009vai.1. mouse.

Organism-specific databases

CTD4761.
MGIMGI:107755. Neurod2.

Phylogenomic databases

eggNOGNOG268401.
GeneTreeENSGT00680000099860.
HOGENOMHOG000049256.
HOVERGENHBG000250.
InParanoidQ62414.
KOK09078.
OMACINGNFS.
OrthoDBEOG722J8S.
PhylomeDBQ62414.
TreeFamTF315153.

Gene expression databases

ArrayExpressQ62414.
BgeeQ62414.
CleanExMM_NEUROD2.
GenevestigatorQ62414.

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

ChiTaRSNEUROD2. mouse.
NextBio293041.
PROQ62414.
SOURCESearch...

Entry information

Entry nameNDF2_MOUSE
AccessionPrimary (citable) accession number: Q62414
Secondary accession number(s): Q61952, Q925V5
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: October 10, 2003
Last modified: July 9, 2014
This is version 118 of the entry and version 3 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

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot