NDF2_HUMAN
ID NDF2_HUMAN Reviewed; 382 AA.
AC Q15784; Q8TBI7; Q9UQC6;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 2.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Neurogenic differentiation factor 2;
DE Short=NeuroD2;
DE AltName: Full=Class A basic helix-loop-helix protein 1;
DE Short=bHLHa1;
DE AltName: Full=NeuroD-related factor;
DE Short=NDRF;
GN Name=NEUROD2; Synonyms=BHLHA1, NDRF;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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 336-338.
RA Tapscott S.J., Tamimi R.T., McCormick B.M.;
RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10209266; DOI=10.1016/s0167-4781(99)00038-x;
RA Kitamura T., Miyachi T., Nakamura S., Kawakami H.;
RT "Identification and analysis of the promoter region of the human NeuroD-
RT related factor (NDRF).";
RL Biochim. Biophys. Acta 1445:142-147(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC 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 [5]
RP INVOLVEMENT IN DEE72, AND VARIANTS DEE72 GLN-130 AND THR-134.
RX PubMed=30323019; DOI=10.1136/jmedgenet-2018-105322;
RA Sega A.G., Mis E.K., Lindstrom K., Mercimek-Andrews S., Ji W., Cho M.T.,
RA Juusola J., Konstantino M., Jeffries L., Khokha M.K., Lakhani S.A.;
RT "De novo pathogenic variants in neuronal differentiation factor 2 (NEUROD2)
RT cause a form of early infantile epileptic encephalopathy.";
RL J. Med. Genet. 56:113-122(2019).
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 (By similarity). {ECO:0000250}.
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 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981}.
CC -!- DOMAIN: The C-terminal region is necessary for depolarization-induced
CC and calcium-dependent transcription activation. {ECO:0000250}.
CC -!- DISEASE: Developmental and epileptic encephalopathy 72 (DEE72)
CC [MIM:618374]: A form of epileptic encephalopathy, a heterogeneous group
CC of severe early-onset epilepsies characterized by refractory seizures,
CC neurodevelopmental impairment, and poor prognosis. Development is
CC normal prior to seizure onset, after which cognitive and motor delays
CC become apparent. DEE72 is an autosomal dominant form with variable
CC severity and onset in infancy. {ECO:0000269|PubMed:30323019}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U58681; AAC26058.1; -; Genomic_DNA.
DR EMBL; AB021742; BAA77569.1; -; mRNA.
DR EMBL; BC022481; AAH22481.1; -; mRNA.
DR CCDS; CCDS11338.1; -.
DR PIR; G02668; G02668.
DR RefSeq; NP_006151.3; NM_006160.3.
DR AlphaFoldDB; Q15784; -.
DR SMR; Q15784; -.
DR BioGRID; 110834; 6.
DR IntAct; Q15784; 4.
DR MINT; Q15784; -.
DR STRING; 9606.ENSP00000306754; -.
DR iPTMnet; Q15784; -.
DR PhosphoSitePlus; Q15784; -.
DR BioMuta; NEUROD2; -.
DR DMDM; 6226655; -.
DR MassIVE; Q15784; -.
DR PaxDb; Q15784; -.
DR PeptideAtlas; Q15784; -.
DR PRIDE; Q15784; -.
DR ProteomicsDB; 60759; -.
DR Antibodypedia; 16207; 207 antibodies from 33 providers.
DR DNASU; 4761; -.
DR Ensembl; ENST00000302584.5; ENSP00000306754.4; ENSG00000171532.5.
DR GeneID; 4761; -.
DR KEGG; hsa:4761; -.
DR MANE-Select; ENST00000302584.5; ENSP00000306754.4; NM_006160.4; NP_006151.3.
DR UCSC; uc002hry.4; human.
DR CTD; 4761; -.
DR DisGeNET; 4761; -.
DR GeneCards; NEUROD2; -.
DR HGNC; HGNC:7763; NEUROD2.
DR HPA; ENSG00000171532; Group enriched (brain, choroid plexus).
DR MalaCards; NEUROD2; -.
DR MIM; 601725; gene.
DR MIM; 618374; phenotype.
DR neXtProt; NX_Q15784; -.
DR OpenTargets; ENSG00000171532; -.
DR Orphanet; 1934; Early infantile epileptic encephalopathy.
DR PharmGKB; PA31565; -.
DR VEuPathDB; HostDB:ENSG00000171532; -.
DR eggNOG; KOG3898; Eukaryota.
DR GeneTree; ENSGT00940000160871; -.
DR HOGENOM; CLU_055134_0_1_1; -.
DR InParanoid; Q15784; -.
DR OMA; KMTQARI; -.
DR OrthoDB; 1096531at2759; -.
DR PhylomeDB; Q15784; -.
DR TreeFam; TF315153; -.
DR PathwayCommons; Q15784; -.
DR SignaLink; Q15784; -.
DR SIGNOR; Q15784; -.
DR BioGRID-ORCS; 4761; 20 hits in 1085 CRISPR screens.
DR ChiTaRS; NEUROD2; human.
DR GeneWiki; NEUROD2; -.
DR GenomeRNAi; 4761; -.
DR Pharos; Q15784; Tbio.
DR PRO; PR:Q15784; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q15784; protein.
DR Bgee; ENSG00000171532; Expressed in cortical plate and 52 other tissues.
DR Genevisible; Q15784; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0070888; F:E-box binding; ISS:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0008306; P:associative learning; IEA:Ensembl.
DR GO; GO:0001662; P:behavioral fear response; IEA:Ensembl.
DR GO; GO:0071277; P:cellular response to calcium ion; ISS:UniProtKB.
DR GO; GO:0071257; P:cellular response to electrical stimulus; ISS:UniProtKB.
DR GO; GO:0021695; P:cerebellar cortex development; ISS:UniProtKB.
DR GO; GO:2000297; P:negative regulation of synapse maturation; ISS:UniProtKB.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0048666; P:neuron development; IEA:Ensembl.
DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; ISS:UniProtKB.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; ISS:UniProtKB.
DR GO; GO:0090129; P:positive regulation of synapse maturation; ISS:UniProtKB.
DR GO; GO:0031915; P:positive regulation of synaptic plasticity; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; ISS: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; Disease variant;
KW DNA-binding; Epilepsy; Neurogenesis; Nucleus; Reference proteome;
KW Transcription; Transcription regulation.
FT CHAIN 1..382
FT /note="Neurogenic differentiation factor 2"
FT /id="PRO_0000127387"
FT DOMAIN 121..173
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 1..129
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 107..113
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 35..53
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 77..95
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 103..120
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 130
FT /note="E -> Q (in DEE72; dbSNP:rs1323339153)"
FT /evidence="ECO:0000269|PubMed:30323019"
FT /id="VAR_082114"
FT VARIANT 134
FT /note="M -> T (in DEE72; dbSNP:rs1567841596)"
FT /evidence="ECO:0000269|PubMed:30323019"
FT /id="VAR_082115"
FT CONFLICT 104
FT /note="R -> G (in Ref. 4; AAH22481)"
FT /evidence="ECO:0000305"
FT CONFLICT 337..338
FT /note="PT -> H (in Ref. 3; BAA77569)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 382 AA; 41361 MW; E33AA5C0BE371B47 CRC64;
MLTRLFSEPG LLSDVPKFAS WGDGEDDEPR SDKGDAPPPP PPAPGPGAPG PARAAKPVPL
RGEEGTEATL AEVKEEGELG GEEEEEEEEE EGLDEAEGER PKKRGPKKRK MTKARLERSK
LRRQKANARE RNRMHDLNAA LDNLRKVVPC YSKTQKLSKI ETLRLAKNYI WALSEILRSG
KRPDLVSYVQ TLCKGLSQPT TNLVAGCLQL NSRNFLTEQG ADGAGRFHGS GGPFAMHPYP
YPCSRLAGAQ CQAAGGLGGG AAHALRTHGY CAAYETLYAA AGGGGASPDY NSSEYEGPLS
PPLCLNGNFS LKQDSSPDHE KSYHYSMHYS ALPGSRPTGH GLVFGSSAVR GGVHSENLLS
YDMHLHHDRG PMYEELNAFF HN
