NDF2_MOUSE
ID NDF2_MOUSE Reviewed; 383 AA.
AC Q62414; Q61952; Q925V5;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 10-OCT-2003, sequence version 3.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Neurogenic differentiation factor 2;
DE Short=NeuroD2;
DE AltName: Full=NeuroD-related factor;
DE Short=NDRF;
GN Name=Neurod2; Synonyms=Ndrf;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8816493; DOI=10.1128/mcb.16.10.5792;
RA McCormick M.B., Tamimi R.M., Snider L., Asakura A., Bergstrom D.,
RA Tapscott S.J.;
RT "NeuroD2 and neuroD3: distinct expression patterns and transcriptional
RT activation potentials within the neuroD gene family.";
RL Mol. Cell. Biol. 16:5792-5800(1996).
RN [2]
RP SEQUENCE REVISION TO 338-339.
RA Tapscott S.J., McCormick M.B., Tamimi R.T.;
RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Embryo;
RX PubMed=8607837; DOI=10.1006/bbrc.1996.0476;
RA Yasunami M., Suzuki K., Maruyama H., Kawakami H., Nagai Y., Hagiwara M.,
RA Ohkubo H.;
RT "Molecular cloning and characterization of a cDNA encoding a novel basic
RT helix-loop-helix protein structurally related to Neuro-D/BHF1.";
RL Biochem. Biophys. Res. Commun. 220:754-758(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=10814830; DOI=10.1016/s0169-328x(00)00038-3;
RA Oda H., Iwata I., Yasunami M., Ohkubo H.;
RT "Structure of the mouse NDRF gene and its regulation during neuronal
RT differentiation of P19 cells.";
RL Brain Res. Mol. Brain Res. 77:37-46(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION, MUTAGENESIS OF 131-GLU-ARG-132, AND SUBCELLULAR LOCATION.
RX PubMed=10648228; DOI=10.1242/dev.127.4.693;
RA Farah M.H., Olson J.M., Sucic H.B., Hume R.I., Tapscott S.J., Turner D.L.;
RT "Generation of neurons by transient expression of neural bHLH proteins in
RT mammalian cells.";
RL Development 127:693-702(2000).
RN [7]
RP DISRUPTION PHENOTYPE.
RX PubMed=11356028; DOI=10.1006/dbio.2001.0245;
RA Olson J.M., Asakura A., Snider L., Hawkes R., Strand A., Stoeck J.,
RA Hallahan A., Pritchard J., Tapscott S.J.;
RT "NeuroD2 is necessary for development and survival of central nervous
RT system neurons.";
RL Dev. Biol. 234:174-187(2001).
RN [8]
RP FUNCTION, DNA-BINDING, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=14697366; DOI=10.1016/j.ydbio.2003.08.027;
RA Lin C.H., Stoeck J., Ravanpay A.C., Guillemot F., Tapscott S.J.,
RA Olson J.M.;
RT "Regulation of neuroD2 expression in mouse brain.";
RL Dev. Biol. 265:234-245(2004).
RN [9]
RP FUNCTION, CHROMATIN-BINDING, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=16203979; DOI=10.1073/pnas.0506785102;
RA Lin C.H., Hansen S., Wang Z., Storm D.R., Tapscott S.J., Olson J.M.;
RT "The dosage of the neuroD2 transcription factor regulates amygdala
RT development and emotional learning.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:14877-14882(2005).
RN [10]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=16504944; DOI=10.1016/j.neuron.2006.01.031;
RA Ince-Dunn G., Hall B.J., Hu S.C., Ripley B., Huganir R.L., Olson J.M.,
RA Tapscott S.J., Ghosh A.;
RT "Regulation of thalamocortical patterning and synaptic maturation by
RT NeuroD2.";
RL Neuron 49:683-695(2006).
RN [11]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16730830; DOI=10.1016/j.jbiotec.2006.04.021;
RA Noda T., Kawamura R., Funabashi H., Mie M., Kobatake E.;
RT "Transduction of NeuroD2 protein induced neural cell differentiation.";
RL J. Biotechnol. 126:230-236(2006).
RN [12]
RP FUNCTION, INTERACTION WITH TCF3; TCF4 AND TCF12, DNA-BINDING, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=18214987; DOI=10.1002/jnr.21615;
RA Ravanpay A.C., Olson J.M.;
RT "E protein dosage influences brain development more than family member
RT identity.";
RL J. Neurosci. Res. 86:1472-1481(2008).
RN [13]
RP FUNCTION, INTERACTION WITH CDC20, AND UBIQUITINATION.
RX PubMed=19900895; DOI=10.1126/science.1177087;
RA Yang Y., Kim A.H., Yamada T., Wu B., Bilimoria P.M., Ikeuchi Y.,
RA de la Iglesia N., Shen J., Bonni A.;
RT "A Cdc20-APC ubiquitin signaling pathway regulates presynaptic
RT differentiation.";
RL Science 326:575-578(2009).
RN [14]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=20346398; DOI=10.1016/j.mcn.2010.03.006;
RA Ravanpay A.C., Hansen S.J., Olson J.M.;
RT "Transcriptional inhibition of REST by NeuroD2 during neuronal
RT differentiation.";
RL Mol. Cell. Neurosci. 44:178-189(2010).
CC -!- FUNCTION: Transcriptional regulator implicated in neuronal
CC determination. Mediates calcium-dependent transcription activation by
CC binding to E box-containing promoter. Critical factor essential for the
CC repression of the genetic program for neuronal differentiation;
CC prevents the formation of synaptic vesicle clustering at active zone to
CC the presynaptic membrane in postmitotic neurons. Induces transcription
CC of ZEB1, which in turn represses neuronal differentiation by down-
CC regulating REST expression. Plays a role in the establishment and
CC maturation of thalamocortical connections; involved in the segregation
CC of thalamic afferents into distinct barrel domains within layer VI of
CC the somatosensory cortex. Involved in the development of the cerebellar
CC and hippocampal granular neurons, neurons in the basolateral nucleus of
CC amygdala and the hypothalamic-pituitary axis. Associates with chromatin
CC to the DPYSL3 E box-containing promoter. {ECO:0000269|PubMed:10648228,
CC ECO:0000269|PubMed:14697366, ECO:0000269|PubMed:16203979,
CC ECO:0000269|PubMed:16504944, ECO:0000269|PubMed:16730830,
CC ECO:0000269|PubMed:18214987, ECO:0000269|PubMed:19900895,
CC ECO:0000269|PubMed:20346398}.
CC -!- SUBUNIT: Interacts with TCF3, TCF4 and TCF12. Interacts with CDC20.
CC Efficient DNA-binding and transcription activation require dimerization
CC with another bHLH protein. {ECO:0000269|PubMed:18214987,
CC ECO:0000269|PubMed:19900895}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981,
CC ECO:0000269|PubMed:10648228, ECO:0000269|PubMed:16730830}.
CC -!- TISSUE SPECIFICITY: Expressed in the external germinal layer (EGL) and
CC internal granular layer (IGL) of the cerebellum (at protein level).
CC Expressed in layers V and VI of the neocortex at postnatal day 1.
CC Expressed in all layers of the neocortex at postnatal day 4. Strongly
CC expressed in layer IV of the neocortex, particularly in the barrel
CC cortex at postnatal day 7. Expressed in the CA1, CA2 and CA3 and
CC dentate gyrus of the hippocampus and many nuclei such as the habenular
CC thalamic nuclei, paraventricular hypothalamic nuclei, amygdala nuclei,
CC and pyramidal nucleus. Expressed in granule cells, molecular layer
CC neurons, and deep cerebella nuclei of the cerebellum. Expressed in
CC brainstem neurons in the external cuneate nucleus and central gray.
CC {ECO:0000269|PubMed:14697366, ECO:0000269|PubMed:16504944,
CC ECO:0000269|PubMed:20346398}.
CC -!- DEVELOPMENTAL STAGE: Expressed in dorsal and ventral parts of the
CC lateral, basolateral and basomedial amygdala at 17 and 18 dpc (at
CC protein level). Initially expressed in embryo at 11 dpc, with
CC persistent expression in the nervous system until birth.
CC {ECO:0000269|PubMed:16203979, ECO:0000269|PubMed:18214987}.
CC -!- DOMAIN: The C-terminal region is necessary for depolarization-induced
CC and calcium-dependent transcription activation.
CC -!- PTM: Ubiquitinated by the APC/C complex; leading to its degradation in
CC neurons. The CDC20-APC/C-induced degradation of NEUROD2 drives
CC presynaptic differentiation. {ECO:0000269|PubMed:19900895}.
CC -!- DISRUPTION PHENOTYPE: Mice exhibit small brains, ataxia, reduced
CC seizure threshold, growth failure, and postnatal premature death. Show
CC excessive apoptosis in central nervous system. Lacks nuclei of the
CC lateral and basolateral amygdala. Organization of cortical neurons into
CC barrel structures is disrupted; thalamocortical axon terminals fail to
CC segregate in the somatosensory cortex. {ECO:0000269|PubMed:11356028,
CC ECO:0000269|PubMed:14697366, ECO:0000269|PubMed:16203979,
CC ECO:0000269|PubMed:16504944}.
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DR EMBL; U58471; AAC26057.1; -; mRNA.
DR EMBL; D83507; BAA11931.1; -; mRNA.
DR EMBL; AB027126; BAA96490.1; -; Genomic_DNA.
DR EMBL; BC058965; AAH58965.1; -; mRNA.
DR CCDS; CCDS25343.1; -.
DR PIR; JC4688; JC4688.
DR RefSeq; NP_035025.3; NM_010895.3.
DR AlphaFoldDB; Q62414; -.
DR STRING; 10090.ENSMUSP00000041373; -.
DR iPTMnet; Q62414; -.
DR PhosphoSitePlus; Q62414; -.
DR MaxQB; Q62414; -.
DR PaxDb; Q62414; -.
DR PRIDE; Q62414; -.
DR ProteomicsDB; 293533; -.
DR Antibodypedia; 16207; 207 antibodies from 33 providers.
DR DNASU; 18013; -.
DR Ensembl; ENSMUST00000041685; ENSMUSP00000041373; ENSMUSG00000038255.
DR GeneID; 18013; -.
DR KEGG; mmu:18013; -.
DR UCSC; uc009vai.1; mouse.
DR CTD; 4761; -.
DR MGI; MGI:107755; Neurod2.
DR VEuPathDB; HostDB:ENSMUSG00000038255; -.
DR eggNOG; KOG3898; Eukaryota.
DR GeneTree; ENSGT00940000160871; -.
DR HOGENOM; CLU_055134_0_1_1; -.
DR InParanoid; Q62414; -.
DR OMA; KMTQARI; -.
DR OrthoDB; 1096531at2759; -.
DR PhylomeDB; Q62414; -.
DR TreeFam; TF315153; -.
DR BioGRID-ORCS; 18013; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Neurod2; mouse.
DR PRO; PR:Q62414; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q62414; protein.
DR Bgee; ENSMUSG00000038255; Expressed in cortical plate and 54 other tissues.
DR ExpressionAtlas; Q62414; baseline and differential.
DR Genevisible; Q62414; MM.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:GO_Central.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0070888; F:E-box binding; IDA:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0008306; P:associative learning; IMP:MGI.
DR GO; GO:0001662; P:behavioral fear response; IMP:MGI.
DR GO; GO:0071277; P:cellular response to calcium ion; IDA:UniProtKB.
DR GO; GO:0071257; P:cellular response to electrical stimulus; IDA:UniProtKB.
DR GO; GO:0021695; P:cerebellar cortex development; IMP:UniProtKB.
DR GO; GO:2000297; P:negative regulation of synapse maturation; IDA:UniProtKB.
DR GO; GO:0048666; P:neuron development; IMP:MGI.
DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; IDA:UniProtKB.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IDA:UniProtKB.
DR GO; GO:0090129; P:positive regulation of synapse maturation; IMP:UniProtKB.
DR GO; GO:0031915; P:positive regulation of synaptic plasticity; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR032649; Neurod2.
DR InterPro; IPR022575; Neurogenic_DUF.
DR InterPro; IPR016637; TF_bHLH_NeuroD.
DR PANTHER; PTHR19290:SF83; PTHR19290:SF83; 1.
DR Pfam; PF00010; HLH; 1.
DR Pfam; PF12533; Neuro_bHLH; 1.
DR PIRSF; PIRSF015618; bHLH_NeuroD; 1.
DR SMART; SM00353; HLH; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
PE 1: Evidence at protein level;
KW Activator; Developmental protein; Differentiation; DNA-binding;
KW Neurogenesis; Nucleus; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..383
FT /note="Neurogenic differentiation factor 2"
FT /id="PRO_0000127388"
FT DOMAIN 122..174
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 1..130
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 108..114
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 20..34
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 78..96
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 104..121
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 131..132
FT /note="ER->AQ: Inhibits neurons differentiation."
FT /evidence="ECO:0000269|PubMed:10648228"
FT CONFLICT 41
FT /note="P -> S (in Ref. 1; AAC26057)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 383 AA; 41493 MW; 68342005219829B1 CRC64;
MLTRLFSEPG LLSDVPKFAS WGDGDDDEPR SDKGDAPPQP PPAPGSGAPG PARAAKPVSL
RGGEEIPEPT LAEVKEEGEL GGEEEEEEEE EEGLDEAEGE RPKKRGPKKR KMTKARLERS
KLRRQKANAR ERNRMHDLNA ALDNLRKVVP CYSKTQKLSK IETLRLAKNY IWALSEILRS
GKRPDLVSYV QTLCKGLSQP TTNLVAGCLQ LNSRNFLTEQ GADGAGRFHG SGGPFAMHPY
PYPCSRLAGA QCQAAGGLGG GAAHALRTHG YCAAYETLYA AAGGGGASPD YNSSEYEGPL
SPPLCLNGNF SLKQDSSPDH EKSYHYSMHY SALPGSRPTG HGLVFGSSAV RGGVHSENLL
SYDMHLHHDR GPMYEELNAF FHN
