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 24-JAN-2024, entry version 162. 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}. 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; 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; 10116-ENSRNOP00000007662; -. DR Ensembl; ENSRNOT00000007662.8; ENSRNOP00000007662.5; ENSRNOG00000005609.8. DR Ensembl; ENSRNOT00055036883; ENSRNOP00055029971; ENSRNOG00055021577. DR Ensembl; ENSRNOT00060025223; ENSRNOP00060020099; ENSRNOG00060014755. DR Ensembl; ENSRNOT00065040696; ENSRNOP00065033185; ENSRNOG00065023756. DR GeneID; 29458; -. DR KEGG; rno:29458; -. DR UCSC; RGD:3165; rat. DR AGR; RGD:3165; -. 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; SFKHEPA; -. DR OrthoDB; 2915590at2759; -. DR PhylomeDB; Q64289; -. DR TreeFam; TF315153; -. DR PRO; PR:Q64289; -. DR Proteomes; UP000002494; Chromosome 3. DR Bgee; ENSRNOG00000005609; Expressed in cerebellum and 8 other cell types or tissues. 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:0061564; P:axon development; IBA:GO_Central. 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: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:0045893; P:positive regulation of DNA-templated transcription; ISS:UniProtKB. 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:0007259; P:receptor signaling pathway via JAK-STAT; ISO:RGD. 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:0009749; P:response to glucose; ISO:RGD. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD. DR GO; GO:0007423; P:sensory organ development; IBA:GO_Central. 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; ISO:RGD. DR CDD; cd19719; bHLH_TS_NeuroD1; 1. DR Gene3D; 4.10.280.10; Helix-loop-helix DNA-binding domain; 1. DR InterPro; IPR011598; bHLH_dom. DR InterPro; IPR036638; HLH_DNA-bd_sf. DR InterPro; IPR022575; NeuroD_DUF. DR InterPro; IPR016637; TF_bHLH_NeuroD. DR PANTHER; PTHR19290; BASIC HELIX-LOOP-HELIX PROTEIN NEUROGENIN-RELATED; 1. DR PANTHER; PTHR19290:SF88; NEUROGENIC DIFFERENTIATION FACTOR 1; 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; HLH, helix-loop-helix DNA-binding domain; 1. DR PROSITE; PS50888; BHLH; 1. DR Genevisible; Q64289; RN. 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 //