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Protein

Neurogenic differentiation factor 2

Gene

Neurod2

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

Functioni

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.8 Publications

GO - Molecular functioni

  • DNA binding Source: MGI
  • E-box binding Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • RNA polymerase II regulatory region sequence-specific DNA binding Source: NTNU_SB
  • transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific DNA binding Source: NTNU_SB
  • transcription corepressor activity Source: UniProtKB

GO - Biological processi

  • associative learning Source: MGI
  • behavioral fear response Source: MGI
  • cellular response to calcium ion Source: UniProtKB
  • cellular response to electrical stimulus Source: UniProtKB
  • cerebellar cortex development Source: UniProtKB
  • negative regulation of synapse maturation Source: UniProtKB
  • neuron development Source: MGI
  • positive regulation of calcium-mediated signaling Source: UniProtKB
  • positive regulation of DNA binding transcription factor activity Source: UniProtKB
  • positive regulation of neuron differentiation Source: UniProtKB
  • positive regulation of synapse maturation Source: UniProtKB
  • positive regulation of synaptic plasticity Source: UniProtKB
  • positive regulation of transcription by RNA polymerase II Source: NTNU_SB
  • protein ubiquitination Source: UniProtKB

Keywordsi

Molecular functionActivator, Developmental protein, DNA-binding
Biological processDifferentiation, Neurogenesis, Transcription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
Neurogenic differentiation factor 2
Short name:
NeuroD2
Alternative name(s):
NeuroD-related factor
Short name:
NDRF
Gene namesi
Name:Neurod2
Synonyms:Ndrf
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:107755 Neurod2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

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.4 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi131 – 132ER → AQ: Inhibits neurons differentiation. 1 Publication2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001273881 – 383Neurogenic differentiation factor 2Add BLAST383

Post-translational modificationi

Ubiquitinated by the APC/C complex; leading to its degradation in neurons. The CDC20-APC/C-induced degradation of NEUROD2 drives presynaptic differentiation.1 Publication

Keywords - PTMi

Ubl conjugation

Proteomic databases

MaxQBiQ62414
PaxDbiQ62414
PRIDEiQ62414

PTM databases

iPTMnetiQ62414
PhosphoSitePlusiQ62414

Expressioni

Tissue specificityi

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.3 Publications

Developmental stagei

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.2 Publications

Gene expression databases

BgeeiENSMUSG00000038255
CleanExiMM_NEUROD2
ExpressionAtlasiQ62414 baseline and differential
GenevisibleiQ62414 MM

Interactioni

Subunit structurei

Interacts with TCF3, TCF4 and TCF12. Interacts with CDC20. Efficient DNA-binding and transcription activation require dimerization with another bHLH protein.2 Publications

GO - Molecular functioni

  • protein heterodimerization activity Source: UniProtKB

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000041373

Structurei

3D structure databases

ProteinModelPortaliQ62414
SMRiQ62414
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini122 – 174bHLHPROSITE-ProRule annotationAdd BLAST53

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi108 – 114Nuclear localization signalSequence analysis7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi83 – 92Poly-Glu10
Compositional biasi283 – 286Poly-Gly4

Domaini

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

Phylogenomic databases

eggNOGiKOG3898 Eukaryota
ENOG4111U26 LUCA
GeneTreeiENSGT00680000099860
HOGENOMiHOG000049256
HOVERGENiHBG000250
InParanoidiQ62414
KOiK09078
OMAiCINGNFS
OrthoDBiEOG091G15AI
PhylomeDBiQ62414
TreeFamiTF315153

Family and domain databases

CDDicd00083 HLH, 1 hit
Gene3Di4.10.280.10, 1 hit
InterProiView protein in InterPro
IPR011598 bHLH_dom
IPR036638 HLH_DNA-bd_sf
IPR032649 Neurod2
IPR022575 Neurogenic_DUF
IPR016637 TF_bHLH_NeuroD
PANTHERiPTHR19290:SF83 PTHR19290:SF83, 1 hit
PfamiView protein in Pfam
PF00010 HLH, 1 hit
PF12533 Neuro_bHLH, 1 hit
PIRSFiPIRSF015618 bHLH_NeuroD, 1 hit
SMARTiView protein in SMART
SM00353 HLH, 1 hit
SUPFAMiSSF47459 SSF47459, 1 hit
PROSITEiView protein in PROSITE
PS50888 BHLH, 1 hit

Sequencei

Sequence statusi: Complete.

Q62414-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLTRLFSEPG LLSDVPKFAS WGDGDDDEPR SDKGDAPPQP PPAPGSGAPG
60 70 80 90 100
PARAAKPVSL RGGEEIPEPT LAEVKEEGEL GGEEEEEEEE EEGLDEAEGE
110 120 130 140 150
RPKKRGPKKR KMTKARLERS KLRRQKANAR ERNRMHDLNA ALDNLRKVVP
160 170 180 190 200
CYSKTQKLSK IETLRLAKNY IWALSEILRS GKRPDLVSYV QTLCKGLSQP
210 220 230 240 250
TTNLVAGCLQ LNSRNFLTEQ GADGAGRFHG SGGPFAMHPY PYPCSRLAGA
260 270 280 290 300
QCQAAGGLGG GAAHALRTHG YCAAYETLYA AAGGGGASPD YNSSEYEGPL
310 320 330 340 350
SPPLCLNGNF SLKQDSSPDH EKSYHYSMHY SALPGSRPTG HGLVFGSSAV
360 370 380
RGGVHSENLL SYDMHLHHDR GPMYEELNAF FHN
Length:383
Mass (Da):41,493
Last modified:October 10, 2003 - v3
Checksum:i68342005219829B1
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti41P → S in AAC26057 (PubMed:8816493).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U58471 mRNA Translation: AAC26057.1
D83507 mRNA Translation: BAA11931.1
AB027126 Genomic DNA Translation: BAA96490.1
BC058965 mRNA Translation: AAH58965.1
CCDSiCCDS25343.1
PIRiJC4688
RefSeqiNP_035025.3, NM_010895.3
UniGeneiMm.4814

Genome annotation databases

EnsembliENSMUST00000041685; ENSMUSP00000041373; ENSMUSG00000038255
GeneIDi18013
KEGGimmu:18013
UCSCiuc009vai.1 mouse

Similar proteinsi

Entry informationi

Entry nameiNDF2_MOUSE
AccessioniPrimary (citable) accession number: Q62414
Secondary accession number(s): Q61952, Q925V5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: October 10, 2003
Last modified: March 28, 2018
This is version 139 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health