Q64289 (NDF1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Neurogenic differentiation factor 1
Short name=NeuroD1

Alternative name(s):
Basic helix-loop-helix factor 1
Short name=BHF-1

Gene names

Name:	Neurod1
Synonyms:	Neurod

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	357 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Acts as a transcriptional activator: mediates transcriptional activation by binding to E box-containing promoter consensus core sequences 5'-CANNTG-3'. Associates with the p300/CBP transcription coactivator complex to stimulate transcription of the secretin gene as well as the gene encoding the cyclin-dependent kinase inhibitor CDKN1A. Contributes to the regulation of several cell differentiation pathways, like those that promote the formation of early retinal ganglion cells, inner ear sensory neurons, granule cells forming either the cerebellum or the dentate gyrus cell layer of the hippocampus, endocrine islet cells of the pancreas and enteroendocrine cells of the small intestine. Together with PAX6 or SIX3, is required for the regulation of amacrine cell fate specification. Also required for dendrite morphogenesis and maintenance in the cerebellar cortex. Associates with chromatin to enhancer regulatory elements in genes encoding key transcriptional regulators of neurogenesis By similarity. Ref.7
Subunit structure	Heterodimer with TCF3/E47; the heterodimer is inhibited in presence of ID2, but not NR0B2, to E-box element. Interacts (via helix-loop-helix motif domain) with EP300 (via C-terminus); the interaction is inhibited by NR0B2. Interacts with TCF3; the interaction is inhibited by ID2. Interacts with RREB1 By similarity. Efficient DNA-binding requires dimerization with another bHLH protein. Heterodimer with TCF3/E47.
Subcellular location	Cytoplasm. Nucleus. Note: Colocalizes with NR0B2 in the nucleus By similarity. In pancreatic islet cells, shuttles to the nucleus in response to glucose stimulation. Ref.6
Induction	Up-regulated by fentanyl. Down-regulated by miR-190. Ref.8
Post-translational modification	Phosphorylated by MAPK1; phosphorylation regulates heterodimerization and DNA-binding activities. Phosphorylation on Ser-266 and Ser-274 increases transactivation on the insulin promoter in glucose-stimulated insulinoma cells By similarity. Phosphorylated. In islet cells, phosphorylated on Ser-274 upon glucose stimulation; which may be required for nuclear localization. In activated neurons, phosphorylated on Ser-336 by CaMK2; which promotes dendritic growth. Ref.6 Ref.7
Sequence similarities	Contains 1 bHLH (basic helix-loop-helix) domain.

Ontologies

Keywords
Biological process	Differentiation Neurogenesis Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Ligand	DNA-binding
Molecular function	Activator Developmental protein
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	amacrine cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB anterior/posterior pattern specification Inferred from electronic annotation. Source: Compara cellular response to glucose stimulus Inferred from direct assay Ref.6. Source: UniProtKB cerebellum development Inferred from expression pattern PubMed 12242038. Source: RGD dentate gyrus development Inferred from sequence or structural similarity. Source: UniProtKB embryonic organ morphogenesis Inferred from electronic annotation. Source: Compara endocrine pancreas development Inferred from sequence or structural similarity. Source: UniProtKB enteroendocrine cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB inner ear development Inferred from sequence or structural similarity. Source: UniProtKB insulin secretion Inferred from electronic annotation. Source: Compara negative regulation of JAK-STAT cascade Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Inferred from electronic annotation. Source: Compara nitric oxide mediated signal transduction Inferred from electronic annotation. Source: Compara nucleocytoplasmic transport Inferred from direct assay Ref.6. Source: UniProtKB pancreatic A cell fate commitment Inferred from electronic annotation. Source: Compara pancreatic PP cell fate commitment Inferred from electronic annotation. Source: Compara positive regulation of apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of neuron differentiation Inferred from direct assay Ref.2. Source: RGD positive regulation of sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay Ref.6. Source: UniProtKB positive regulation of transcription regulatory region DNA binding Inferred from electronic annotation. Source: Compara regulation of cell cycle arrest Inferred from sequence or structural similarity. Source: UniProtKB regulation of intestinal epithelial structure maintenance Inferred from sequence or structural similarity. Source: UniProtKB response to drug Inferred from expression pattern PubMed 16635253. Source: RGD signal transduction involved in regulation of gene expression Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm Inferred from direct assay Ref.6. Source: UniProtKB nucleus Inferred from direct assay Ref.6. Source: UniProtKB
Molecular_function	E-box binding Inferred from electronic annotation. Source: Compara RNA polymerase II transcription coactivator activity Inferred from electronic annotation. Source: Compara chromatin binding Inferred from sequence or structural similarity. Source: UniProtKB double-stranded DNA binding Inferred from direct assay Ref.2. Source: RGD sequence-specific DNA binding Inferred from electronic annotation. Source: Compara sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 357	357	Neurogenic differentiation factor 1		PRO_0000127384
Regions
	Domain	101 – 153	53	bHLH
	Motif	87 – 93	7	Nuclear localization signal Potential
	Compositional bias	58 – 77	20	Glu-rich (acidic)
	Compositional bias	67 – 76	10	Poly-Glu
	Compositional bias	87 – 90	4	Poly-Lys
Amino acid modifications
	Modified residue	162	1	Phosphoserine By similarity
	Modified residue	259	1	Phosphoserine By similarity
	Modified residue	266	1	Phosphoserine By similarity
	Modified residue	274	1	Phosphoserine Probable
	Modified residue	336	1	Phosphoserine; by CaMK2 Ref.7
Experimental info
	Mutagenesis	259	1	S → A: No effect on subcellular location. Ref.6
	Mutagenesis	262	1	T → A: No effect on subcellular location. Ref.6
	Mutagenesis	266	1	S → A: No effect on subcellular location. Ref.6
	Mutagenesis	274	1	S → A: Impairs translocation from the cytoplasm to the nucleus upon glucose stimulation. Ref.6
	Mutagenesis	274	1	S → D: No effect on subcellular location. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Q64289 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: F773637E64D3E99E	FASTA	357	40,001
	10 20 30 40 50 60 MTKSYSESGL MGEPQPQGPP SWTDECLSSQ DEEHEADKKE DELEAMNAEE DSLRNGGEEE 70 80 90 100 110 120 DEDEDLEEEE EEEEEEDDQK PKRRGPKKKK MTKARLERFK LRRMKANARE RNRMHGLNAA 130 140 150 160 170 180 LDNLRKVVPC YSKTQKLSKI ETLRLAKNYI WALSEILRSG KSPDLVSFVQ TLCKGLSQPT 190 200 210 220 230 240 TNLVAGCLQL NPRTFLPEQN PDMPPHLPTA SASFPVHPYS YQSPGLPSPP YGTMDSSHVF 250 260 270 280 290 300 HVKPPPHAYS AALEPFFESP LTDCTSPSFD GPLSPPLSIN GNFSFKHEPS TEFEKNYAFT 310 320 330 340 350 MHYPAATLAG PQSHGSIFSS GAAAPRCEIP IDNIMSFDSH SHHERVMSAQ LNAIFHD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression of a rat brain basic helix-loop-helix factor." Kawakami H., Maruyama H., Yasunami M., Ohkubo H., Hara H., Saida T., Nakanishi S., Nakamura S. Biochem. Biophys. Res. Commun. 221:199-204(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Cerebellum.
[2]	"Overexpression of NeuroD in PC12 cells alters morphology and enhances expression of the adenylate kinase isozyme 1 gene." Noma T., Yoon Y.S., Nakazawa A. Brain Res. Mol. Brain Res. 67:53-63(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[3]	"Cloning of rat NeuroD/Beta2." Andersen F.G., Madsen O.D., Serup P. Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: New England Deaconess Hospital. Tissue: Pancreatic islet.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[5]	"Developmental expression of neurogenic gene, NeuroD in the mammalian retina." Ahmad I., Acharay H.R. Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 88-200. Strain: Sprague-Dawley. Tissue: Retina.
[6]	"Glucose induced MAPK signalling influences NeuroD1-mediated activation and nuclear localization." Petersen H.V., Jensen J.N., Stein R., Serup P. FEBS Lett. 528:241-245(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF SER-259; THR-262; SER-266 AND SER-274, PHOSPHORYLATION AT SER-274.
[7]	"A CaMKII-NeuroD signaling pathway specifies dendritic morphogenesis." Gaudilliere B., Konishi Y., de la Iglesia N., Yao G., Bonni A. Neuron 41:229-241(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT SER-336.
[8]	"Modulations of NeuroD activity contribute to the differential effects of morphine and fentanyl on dendritic spine stability." Zheng H., Zeng Y., Chu J., Kam A.Y., Loh H.H., Law P.Y. J. Neurosci. 30:8102-8110(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D82075 mRNA. Translation: BAA11536.1. D82074 mRNA. Translation: BAA11535.1. D82945 mRNA. Translation: BAA81821.1. AF107728 mRNA. Translation: AAD19609.1. BC092367 mRNA. Translation: AAH92367.1. BC094526 mRNA. Translation: AAH94526.1. U80603 mRNA. Translation: AAB38744.1.
IPI	IPI00211014.
PIR	JC4703.
RefSeq	NP_062091.1. NM_019218.2.
UniGene	Rn.44289.
3D structure databases
ProteinModelPortal	Q64289.
ModBase	Search...
PTM databases
PhosphoSite	Q64289.
Proteomic databases
PaxDb	Q64289.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000007662; ENSRNOP00000007662; ENSRNOG00000005609.
GeneID	29458.
KEGG	rno:29458.
UCSC	RGD:3165. rat.
Organism-specific databases
CTD	4760.
RGD	3165. Neurod1.
Phylogenomic databases
eggNOG	NOG287211.
GeneTree	ENSGT00680000099860.
HOGENOM	HOG000049256.
HOVERGEN	HBG000250.
InParanoid	Q64289.
KO	K08033.
OMA	DEEHETD.
OrthoDB	EOG44F69G.
Gene expression databases
ArrayExpress	Q64289.
Genevestigator	Q64289.
GermOnline	ENSRNOG00000005609. Rattus norvegicus.
Family and domain databases
Gene3D	4.10.280.10. 1 hit.
InterPro	IPR011598. bHLH_dom. IPR022575. Neurogenic_DUF. IPR016637. TF_bHLH_NeuroD. [Graphical view]
Pfam	PF00010. HLH. 1 hit. PF12533. Neuro_bHLH. 1 hit. [Graphical view]
PIRSF	PIRSF015618. bHLH_NeuroD. 1 hit.
SMART	SM00353. HLH. 1 hit. [Graphical view]
SUPFAM	SSF47459. HLH_basic. 1 hit.
PROSITE	PS50888. BHLH. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	609242.

Entry information

Entry name

NDF1_RAT

Accession

Primary (citable) accession number: Q64289
Secondary accession number(s): Q569P0

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 100 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program