NDF1_RAT
ID NDF1_RAT Reviewed; 357 AA.
AC Q64289; Q569P0;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Neurogenic differentiation factor 1;
DE Short=NeuroD1;
DE AltName: Full=Basic helix-loop-helix factor 1;
DE Short=BHF-1;
GN Name=Neurod1; Synonyms=Neurod;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Cerebellum;
RX PubMed=8660336; DOI=10.1006/bbrc.1996.0569;
RA Kawakami H., Maruyama H., Yasunami M., Ohkubo H., Hara H., Saida T.,
RA Nakanishi S., Nakamura S.;
RT "Cloning and expression of a rat brain basic helix-loop-helix factor.";
RL Biochem. Biophys. Res. Commun. 221:199-204(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=10101232; DOI=10.1016/s0169-328x(99)00038-8;
RA Noma T., Yoon Y.S., Nakazawa A.;
RT "Overexpression of NeuroD in PC12 cells alters morphology and enhances
RT expression of the adenylate kinase isozyme 1 gene.";
RL Brain Res. Mol. Brain Res. 67:53-63(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=New England Deaconess Hospital; TISSUE=Pancreatic islet;
RA Andersen F.G., Madsen O.D., Serup P.;
RT "Cloning of rat NeuroD/Beta2.";
RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases.
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 NUCLEOTIDE SEQUENCE [MRNA] OF 88-200.
RC STRAIN=Sprague-Dawley; TISSUE=Retina;
RA Ahmad I., Acharay H.R.;
RT "Developmental expression of neurogenic gene, NeuroD in the mammalian
RT retina.";
RL Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP SUBCELLULAR LOCATION, MUTAGENESIS OF SER-259; THR-262; SER-266 AND SER-274,
RP AND PHOSPHORYLATION AT SER-274.
RX PubMed=12297313; DOI=10.1016/s0014-5793(02)03318-5;
RA Petersen H.V., Jensen J.N., Stein R., Serup P.;
RT "Glucose induced MAPK signalling influences NeuroD1-mediated activation and
RT nuclear localization.";
RL FEBS Lett. 528:241-245(2002).
RN [7]
RP FUNCTION, AND PHOSPHORYLATION AT SER-336.
RX PubMed=14741104; DOI=10.1016/s0896-6273(03)00841-9;
RA Gaudilliere B., Konishi Y., de la Iglesia N., Yao G., Bonni A.;
RT "A CaMKII-NeuroD signaling pathway specifies dendritic morphogenesis.";
RL Neuron 41:229-241(2004).
RN [8]
RP INDUCTION.
RX PubMed=20554861; DOI=10.1523/jneurosci.6069-09.2010;
RA Zheng H., Zeng Y., Chu J., Kam A.Y., Loh H.H., Law P.Y.;
RT "Modulations of NeuroD activity contribute to the differential effects of
RT morphine and fentanyl on dendritic spine stability.";
RL J. Neurosci. 30:8102-8110(2010).
CC -!- FUNCTION: Acts as a transcriptional activator: mediates transcriptional
CC activation by binding to E box-containing promoter consensus core
CC sequences 5'-CANNTG-3' (By similarity). Associates with the p300/CBP
CC transcription coactivator complex to stimulate transcription of the
CC secretin gene as well as the gene encoding the cyclin-dependent kinase
CC inhibitor CDKN1A (By similarity). Contributes to the regulation of
CC several cell differentiation pathways, like those that promote the
CC formation of early retinal ganglion cells, inner ear sensory neurons,
CC granule cells forming either the cerebellum or the dentate gyrus cell
CC layer of the hippocampus, endocrine islet cells of the pancreas and
CC enteroendocrine cells of the small intestine (By similarity). Together
CC with PAX6 or SIX3, is required for the regulation of amacrine cell fate
CC specification (By similarity). Also required for dendrite morphogenesis
CC and maintenance in the cerebellar cortex (PubMed:14741104). Associates
CC with chromatin to enhancer regulatory elements in genes encoding key
CC transcriptional regulators of neurogenesis (By similarity).
CC {ECO:0000250|UniProtKB:Q60867, ECO:0000269|PubMed:14741104}.
CC -!- SUBUNIT: Efficient DNA-binding requires dimerization with another bHLH
CC protein. Heterodimer with TCF3/E47; the heterodimer is inhibited in
CC presence of ID2, but not NR0B2, to E-box element. Interacts with EP300;
CC the interaction is inhibited by NR0B2 (By similarity). Interacts with
CC RREB1 (By similarity). Interacts with ATOH8 (By similarity).
CC {ECO:0000250|UniProtKB:Q13562, ECO:0000250|UniProtKB:Q60867}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12297313}. Nucleus
CC {ECO:0000255|PROSITE-ProRule:PRU00981, ECO:0000269|PubMed:12297313}.
CC Note=Colocalizes with NR0B2 in the nucleus (By similarity). In
CC pancreatic islet cells, shuttles to the nucleus in response to glucose
CC stimulation. {ECO:0000250}.
CC -!- INDUCTION: Up-regulated by fentanyl. Down-regulated by miR-190.
CC {ECO:0000269|PubMed:20554861}.
CC -!- PTM: Phosphorylated by MAPK1; phosphorylation regulates
CC heterodimerization and DNA-binding activities. Phosphorylation on Ser-
CC 266 and Ser-274 increases transactivation on the insulin promoter in
CC glucose-stimulated insulinoma cells (By similarity). Phosphorylated. In
CC islet cells, phosphorylated on Ser-274 upon glucose stimulation; which
CC may be required for nuclear localization. In activated neurons,
CC phosphorylated on Ser-336 by CaMK2; which promotes dendritic growth.
CC {ECO:0000250, ECO:0000269|PubMed:12297313,
CC ECO:0000269|PubMed:14741104}.
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DR EMBL; D82075; BAA11536.1; -; mRNA.
DR EMBL; D82074; BAA11535.1; -; mRNA.
DR EMBL; D82945; BAA81821.1; -; mRNA.
DR EMBL; AF107728; AAD19609.1; -; mRNA.
DR EMBL; BC092367; AAH92367.1; -; mRNA.
DR EMBL; BC094526; AAH94526.1; -; mRNA.
DR EMBL; U80603; AAB38744.1; -; mRNA.
DR PIR; JC4703; JC4703.
DR RefSeq; NP_062091.1; NM_019218.2.
DR AlphaFoldDB; Q64289; -.
DR SMR; Q64289; -.
DR BioGRID; 248101; 2.
DR STRING; 10116.ENSRNOP00000007662; -.
DR iPTMnet; Q64289; -.
DR PhosphoSitePlus; Q64289; -.
DR PaxDb; Q64289; -.
DR Ensembl; ENSRNOT00000007662; ENSRNOP00000007662; ENSRNOG00000005609.
DR GeneID; 29458; -.
DR KEGG; rno:29458; -.
DR UCSC; RGD:3165; rat.
DR CTD; 4760; -.
DR RGD; 3165; Neurod1.
DR eggNOG; KOG3898; Eukaryota.
DR GeneTree; ENSGT00940000160478; -.
DR HOGENOM; CLU_055134_0_0_1; -.
DR InParanoid; Q64289; -.
DR OMA; FKHEPAA; -.
DR OrthoDB; 1096531at2759; -.
DR PhylomeDB; Q64289; -.
DR TreeFam; TF315153; -.
DR PRO; PR:Q64289; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000005609; Expressed in cerebellum and 8 other tissues.
DR Genevisible; Q64289; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:RGD.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; ISO:RGD.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0003690; F:double-stranded DNA binding; IDA:RGD.
DR GO; GO:0070888; F:E-box binding; ISO:RGD.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISO:RGD.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:RGD.
DR GO; GO:0035881; P:amacrine cell differentiation; ISS:UniProtKB.
DR GO; GO:0009952; P:anterior/posterior pattern specification; ISO:RGD.
DR GO; GO:0043010; P:camera-type eye development; ISO:RGD.
DR GO; GO:0045165; P:cell fate commitment; ISO:RGD.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IDA:UniProtKB.
DR GO; GO:0021549; P:cerebellum development; IEP:RGD.
DR GO; GO:0021542; P:dentate gyrus development; ISS:UniProtKB.
DR GO; GO:0048562; P:embryonic organ morphogenesis; ISO:RGD.
DR GO; GO:0031018; P:endocrine pancreas development; ISS:UniProtKB.
DR GO; GO:0035883; P:enteroendocrine cell differentiation; ISS:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; ISO:RGD.
DR GO; GO:0030902; P:hindbrain development; ISO:RGD.
DR GO; GO:0048839; P:inner ear development; ISS:UniProtKB.
DR GO; GO:0030073; P:insulin secretion; ISO:RGD.
DR GO; GO:0046426; P:negative regulation of receptor signaling pathway via JAK-STAT; ISO:RGD.
DR GO; GO:2000675; P:negative regulation of type B pancreatic cell apoptotic process; ISO:RGD.
DR GO; GO:0048666; P:neuron development; IEA:InterPro.
DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR GO; GO:0007263; P:nitric oxide mediated signal transduction; ISO:RGD.
DR GO; GO:0006913; P:nucleocytoplasmic transport; IDA:UniProtKB.
DR GO; GO:0003326; P:pancreatic A cell fate commitment; ISO:RGD.
DR GO; GO:0003329; P:pancreatic PP cell fate commitment; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0045597; P:positive regulation of cell differentiation; ISS:UniProtKB.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IDA:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:2000679; P:positive regulation of transcription regulatory region DNA binding; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; IEA:Ensembl.
DR GO; GO:0060730; P:regulation of intestinal epithelial structure maintenance; ISS:UniProtKB.
DR GO; GO:0045664; P:regulation of neuron differentiation; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0009749; P:response to glucose; ISO:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0023019; P:signal transduction involved in regulation of gene expression; ISO:RGD.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR032652; Neurod1.
DR InterPro; IPR022575; Neurogenic_DUF.
DR InterPro; IPR016637; TF_bHLH_NeuroD.
DR PANTHER; PTHR19290:SF88; PTHR19290:SF88; 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; Cytoplasm; Developmental protein; Differentiation; DNA-binding;
KW Neurogenesis; Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..357
FT /note="Neurogenic differentiation factor 1"
FT /id="PRO_0000127384"
FT DOMAIN 101..153
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 1..94
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 87..93
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 27..53
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 54..76
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 162
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60867"
FT MOD_RES 259
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60867"
FT MOD_RES 266
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60867"
FT MOD_RES 274
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:12297313"
FT MOD_RES 336
FT /note="Phosphoserine; by CaMK2"
FT /evidence="ECO:0000269|PubMed:14741104"
FT MUTAGEN 259
FT /note="S->A: No effect on subcellular location."
FT /evidence="ECO:0000269|PubMed:12297313"
FT MUTAGEN 262
FT /note="T->A: No effect on subcellular location."
FT /evidence="ECO:0000269|PubMed:12297313"
FT MUTAGEN 266
FT /note="S->A: No effect on subcellular location."
FT /evidence="ECO:0000269|PubMed:12297313"
FT MUTAGEN 274
FT /note="S->A: Impairs translocation from the cytoplasm to
FT the nucleus upon glucose stimulation."
FT /evidence="ECO:0000269|PubMed:12297313"
FT MUTAGEN 274
FT /note="S->D: No effect on subcellular location."
FT /evidence="ECO:0000269|PubMed:12297313"
SQ SEQUENCE 357 AA; 40001 MW; F773637E64D3E99E CRC64;
MTKSYSESGL MGEPQPQGPP SWTDECLSSQ DEEHEADKKE DELEAMNAEE DSLRNGGEEE
DEDEDLEEEE EEEEEEDDQK PKRRGPKKKK MTKARLERFK LRRMKANARE RNRMHGLNAA
LDNLRKVVPC YSKTQKLSKI ETLRLAKNYI WALSEILRSG KSPDLVSFVQ TLCKGLSQPT
TNLVAGCLQL NPRTFLPEQN PDMPPHLPTA SASFPVHPYS YQSPGLPSPP YGTMDSSHVF
HVKPPPHAYS AALEPFFESP LTDCTSPSFD GPLSPPLSIN GNFSFKHEPS TEFEKNYAFT
MHYPAATLAG PQSHGSIFSS GAAAPRCEIP IDNIMSFDSH SHHERVMSAQ LNAIFHD
