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P35428 (HES1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Transcription factor HES-1
Alternative name(s):
Hairy and enhancer of split 1
Gene names
Name:Hes1
Synonyms:Hes-1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length282 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transcriptional repressor of genes that require a bHLH protein for their transcription. May act as a negative regulator of myogenesis by inhibiting the functions of MYOD1 and ASH1 By similarity. Binds DNA on N-box motifs: 5'-CACNAG-3' with high affinity and on E-box motifs: 5'-CANNTG-3' with low affinity. May play a role in a functional FA core complex response to DNA cross-link damage, being required for the stability and nuclear localization of FA core complex proteins, as well as for FANCD2 monoubiquitination in response to DNA damage By similarity.

Subunit structure

Interacts with SIRT1 By similarity. Transcription repression requires formation of a complex with a corepressor protein of the Groucho/TLE family. Interacts (via WPRW motif) with TLE1, and more weakly with TLE2. Interacts with HES6. Interacts with an FA complex, composed of FANCA, FANCF, FANCG and FANCL, but not of FANCC, nor FANCE By similarity. Ref.3 Ref.4

Subcellular location

Nucleus.

Tissue specificity

Expressed at high levels in undifferentiated neural precursor cells, but the level of expression decreases as neural differentiation proceeds.

Domain

Has a particular type of basic domain (presence of a helix-interrupting proline) that binds to the N-box (CACNAG), rather than the canonical E-box (CANNTG).

The C-terminal WRPW motif is a transcriptional repression domain necessary for the interaction with Groucho/TLE family members, transcriptional corepressors recruited to specific target DNA by Hairy-related proteins.

The bHLH, as well as cooperation between the central Orange domain and the C-terminal WRPW motif, is required for transcriptional repressor activity By similarity.

Sequence similarities

Contains 1 bHLH (basic helix-loop-helix) domain.

Contains 1 Orange domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   LigandDNA-binding
   Molecular functionRepressor
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processNotch signaling pathway

Non-traceable author statement PubMed 15465493. Source: UniProtKB

S-shaped body morphogenesis

Inferred from expression pattern PubMed 15821257. Source: UniProtKB

STAT protein import into nucleus

Inferred from direct assay PubMed 15156153. Source: UniProtKB

adenohypophysis development

Inferred from mutant phenotype PubMed 18996108. Source: MGI

aorta morphogenesis

Inferred from mutant phenotype PubMed 20122914. Source: BHF-UCL

artery morphogenesis

Inferred from mutant phenotype PubMed 20122914. Source: BHF-UCL

ascending aorta morphogenesis

Inferred from mutant phenotype PubMed 19609448. Source: BHF-UCL

auditory receptor cell differentiation

Inferred from mutant phenotype PubMed 11425898. Source: MGI

auditory receptor cell fate determination

Inferred from mutant phenotype PubMed 11425898. Source: MGI

cardiac neural crest cell development involved in outflow tract morphogenesis

Inferred from mutant phenotype PubMed 19609448. Source: MGI

cell adhesion

Inferred from genetic interaction PubMed 15496443. Source: MGI

cell fate commitment

Inferred from mutant phenotype PubMed 10952889. Source: MGI

cell maturation

Inferred from genetic interaction PubMed 15496443. Source: MGI

cell migration

Inferred from genetic interaction PubMed 18996108. Source: MGI

cell morphogenesis involved in neuron differentiation

Inferred from genetic interaction PubMed 11500373. Source: MGI

cochlea development

Inferred from mutant phenotype PubMed 18302773. Source: MGI

comma-shaped body morphogenesis

Inferred from expression pattern PubMed 15821257. Source: UniProtKB

common bile duct development

Inferred from mutant phenotype PubMed 19619492. Source: MGI

embryonic heart tube morphogenesis

Inferred from mutant phenotype PubMed 19609448. Source: BHF-UCL

endocrine pancreas development

Traceable author statement. Source: Reactome

forebrain radial glial cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

glomerulus vasculature development

Inferred from expression pattern PubMed 15821257. Source: UniProtKB

hindbrain morphogenesis

Inferred from genetic interaction PubMed 11500373. Source: MGI

in utero embryonic development

Inferred from genetic interaction PubMed 11500373. Source: MGI

labyrinthine layer blood vessel development

Inferred from mutant phenotype PubMed 20122914. Source: BHF-UCL

lateral inhibition

Inferred from mutant phenotype PubMed 10804175. Source: MGI

liver development

Inferred from mutant phenotype PubMed 15578515. Source: MGI

lung development

Inferred from mutant phenotype PubMed 10952889. Source: MGI

metanephric nephron tubule morphogenesis

Inferred from expression pattern PubMed 15465493. Source: UniProtKB

midbrain development

Inferred from genetic interaction PubMed 11500373. Source: MGI

midbrain-hindbrain boundary morphogenesis

Inferred from genetic interaction PubMed 11500373. Source: MGI

negative regulation of auditory receptor cell differentiation

Inferred from mutant phenotype PubMed 11023859. Source: MGI

negative regulation of cell differentiation

Inferred from mutant phenotype PubMed 10952889PubMed 17426285. Source: MGI

negative regulation of forebrain neuron differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of glial cell proliferation

Inferred from direct assay PubMed 12666205. Source: UniProtKB

negative regulation of inner ear receptor cell differentiation

Inferred from mutant phenotype PubMed 12208538. Source: UniProtKB

negative regulation of neuron differentiation

Inferred from mutant phenotype PubMed 10205173PubMed 16038893. Source: MGI

negative regulation of oligodendrocyte differentiation

Inferred from direct assay PubMed 12666205. Source: UniProtKB

negative regulation of pancreatic A cell differentiation

Inferred from mutant phenotype PubMed 10615124. Source: MGI

negative regulation of pro-B cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of stem cell differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of stomach neuroendocrine cell differentiation

Inferred from mutant phenotype PubMed 18173746. Source: MGI

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 21259317. Source: UniProtKB

negative regulation of transcription, DNA-templated

Inferred from mutant phenotype PubMed 12208538. Source: UniProtKB

neural tube development

Inferred from genetic interaction PubMed 10804175PubMed 11500373. Source: MGI

neuronal stem cell maintenance

Inferred from mutant phenotype PubMed 11399758. Source: UniProtKB

oculomotor nerve development

Inferred from genetic interaction PubMed 11500373. Source: MGI

outflow tract morphogenesis

Inferred from mutant phenotype PubMed 20122914. Source: BHF-UCL

pancreas development

Inferred from mutant phenotype PubMed 19619492. Source: MGI

pattern specification process

Inferred from mutant phenotype PubMed 18302773. Source: MGI

pharyngeal system development

Inferred from mutant phenotype. Source: BHF-UCL

pituitary gland development

Inferred from mutant phenotype PubMed 17015435PubMed 17426285. Source: MGI

positive regulation of BMP signaling pathway

Inferred from genetic interaction PubMed 18579678. Source: MGI

positive regulation of DNA binding

Inferred from direct assay PubMed 15156153. Source: UniProtKB

positive regulation of JAK-STAT cascade

Inferred from direct assay PubMed 15156153. Source: UniProtKB

positive regulation of Notch signaling pathway

Inferred from mutant phenotype PubMed 12208538. Source: UniProtKB

positive regulation of T cell proliferation

Inferred from mutant phenotype PubMed 15870295. Source: MGI

positive regulation of astrocyte differentiation

Inferred from direct assay PubMed 12666205. Source: UniProtKB

positive regulation of cell proliferation

Inferred from mutant phenotype PubMed 20122914. Source: BHF-UCL

positive regulation of mitotic cell cycle, embryonic

Inferred from mutant phenotype PubMed 19609448. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 19609448PubMed 20122914. Source: BHF-UCL

positive regulation of transcription, DNA-templated

Inferred from mutant phenotype PubMed 12208538. Source: UniProtKB

positive regulation of tyrosine phosphorylation of Stat3 protein

Inferred from direct assay PubMed 15156153. Source: UniProtKB

protein complex assembly

Inferred from direct assay PubMed 15156153. Source: UniProtKB

regulation of fat cell differentiation

Inferred from mutant phenotype PubMed 15060169. Source: MGI

regulation of neurogenesis

Inferred from genetic interaction PubMed 10804175PubMed 19050759. Source: MGI

regulation of secondary heart field cardioblast proliferation

Inferred from mutant phenotype PubMed 19609448. Source: MGI

regulation of timing of cell differentiation

Inferred from mutant phenotype PubMed 17015435PubMed 8543157. Source: MGI

regulation of timing of neuron differentiation

Inferred from mutant phenotype PubMed 8543157. Source: MGI

regulation of transcription from RNA polymerase II promoter

Inferred from genetic interaction PubMed 20628571. Source: MGI

renal interstitial cell development

Inferred from expression pattern PubMed 15821257. Source: UniProtKB

smoothened signaling pathway

Inferred from direct assay PubMed 19124651. Source: MGI

somatic stem cell maintenance

Inferred from mutant phenotype PubMed 10615124. Source: MGI

telencephalon development

Inferred from mutant phenotype PubMed 19050759. Source: MGI

thymus development

Inferred from mutant phenotype PubMed 20122914. Source: BHF-UCL

transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 15870295. Source: GOC

trochlear nerve development

Inferred from genetic interaction PubMed 11500373. Source: MGI

ureteric bud morphogenesis

Inferred from expression pattern PubMed 15821257. Source: UniProtKB

vascular smooth muscle cell development

Inferred from mutant phenotype PubMed 20122914. Source: BHF-UCL

ventricular septum development

Inferred from mutant phenotype PubMed 20122914. Source: BHF-UCL

ventricular septum morphogenesis

Inferred from mutant phenotype PubMed 19609448. Source: BHF-UCL

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 15645444. Source: MGI

intracellular

Inferred from direct assay PubMed 16489008. Source: MGI

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay PubMed 12666205PubMed 15156153. Source: UniProtKB

   Molecular_functionDNA binding

Inferred from direct assay Ref.4PubMed 14764602. Source: MGI

N-box binding

Inferred from direct assay PubMed 17681138. Source: UniProtKB

RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription

Inferred from direct assay PubMed 21259317. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 15156153PubMed 17681138PubMed 21259317. Source: UniProtKB

protein homodimerization activity

Inferred from direct assay PubMed 21259317. Source: UniProtKB

sequence-specific DNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

sequence-specific DNA binding RNA polymerase II transcription factor activity

Inferred from direct assay PubMed 15870295. Source: MGI

sequence-specific DNA binding transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

transcription factor binding

Non-traceable author statement PubMed 17611704. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 282282Transcription factor HES-1
PRO_0000127203

Regions

Domain34 – 9158bHLH
Domain110 – 14334Orange
Motif277 – 2804WRPW motif
Compositional bias156 – 24893Pro-rich
Compositional bias251 – 27323Ser/Thr-rich

Sequences

Sequence LengthMass (Da)Tools
P35428 [UniParc].

Last modified June 1, 1994. Version 1.
Checksum: 88C7700C5EF7DA26

FASTA28229,749
        10         20         30         40         50         60 
MPADIMEKNS SSPVAATPAS VNTTPDKPKT ASEHRKSSKP IMEKRRRARI NESLSQLKTL 

        70         80         90        100        110        120 
ILDALKKDSS RHSKLEKADI LEMTVKHLRN LQRAQMTAAL STDPSVLGKY RAGFSECMNE 

       130        140        150        160        170        180 
VTRFLSTCEG VNTEVRTRLL GHLANCMTQI NAMTYPGQAH PALQAPPPPP PSGPAGPQHA 

       190        200        210        220        230        240 
PFAPPPPPLV PIPGGAAPPP GSAPCKLGSQ AGEAAKVFGG FQVVPAPDGQ FAFLIPNGAF 

       250        260        270        280 
AHSGPVIPVY TSNSGTSVGP NAVSPSSGSS LTSDSMWRPW RN 

« Hide

References

« Hide 'large scale' references
[1]"Structure, chromosomal locus, and promoter analysis of the gene encoding the mouse helix-loop-helix factor HES-1. Negative autoregulation through the multiple N box elements."
Takebayashi K., Sasai Y., Sakai Y., Watanabe T., Nakanishi S., Kageyama R.
J. Biol. Chem. 269:5150-5156(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"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].
Strain: FVB/N.
Tissue: Colon and Eye.
[3]"Transducin-like Enhancer of split 2, a mammalian homologue of Drosophila Groucho, acts as a transcriptional repressor, interacts with Hairy/Enhancer of split proteins, and is expressed during neuronal development."
Grbavec D., Lo R., Liu Y., Stifani S.
Eur. J. Biochem. 258:339-349(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TLE1 AND TLE2.
[4]"The bHLH gene Hes6, an inhibitor of Hes1, promotes neuronal differentiation."
Bae S.-K., Bessho Y., Hojo M., Kageyama R.
Development 127:2933-2943(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: DNA-BINDING, INTERACTION WITH HES6.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D16464 Genomic DNA. Translation: BAA03931.1.
BC018375 mRNA. Translation: AAH18375.1.
BC051428 mRNA. Translation: AAH51428.1.
CCDSCCDS28098.1.
PIRA53336.
RefSeqNP_032261.1. NM_008235.2.
UniGeneMm.390859.

3D structure databases

ProteinModelPortalP35428.
SMRP35428. Positions 27-95.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid200275. 5 interactions.

Chemistry

ChEMBLCHEMBL1075292.

PTM databases

PhosphoSiteP35428.

Proteomic databases

PRIDEP35428.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000023171; ENSMUSP00000023171; ENSMUSG00000022528.
GeneID15205.
KEGGmmu:15205.
UCSCuc007ywl.1. mouse.

Organism-specific databases

CTD3280.
MGIMGI:104853. Hes1.

Phylogenomic databases

eggNOGNOG319418.
HOGENOMHOG000236346.
HOVERGENHBG005960.
InParanoidP35428.
KOK06054.
OMAMPADMME.
OrthoDBEOG780RN7.
PhylomeDBP35428.
TreeFamTF351373.

Enzyme and pathway databases

ReactomeREACT_118814. mNICD1 stimulates Hes1 transcription.
REACT_13641. Regulation of Beta-Cell Development.
REACT_188257. Signal Transduction.
REACT_188576. Developmental Biology.

Gene expression databases

ArrayExpressP35428.
BgeeP35428.
CleanExMM_HES1.
GenevestigatorP35428.

Family and domain databases

Gene3D4.10.280.10. 1 hit.
InterProIPR011598. bHLH_dom.
IPR003650. Orange.
IPR018352. Orange_subgr.
[Graphical view]
PfamPF07527. Hairy_orange. 1 hit.
PF00010. HLH. 1 hit.
[Graphical view]
SMARTSM00353. HLH. 1 hit.
SM00511. ORANGE. 1 hit.
[Graphical view]
SUPFAMSSF47459. SSF47459. 1 hit.
PROSITEPS50888. BHLH. 1 hit.
PS51054. ORANGE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio287757.
PROP35428.
SOURCESearch...

Entry information

Entry nameHES1_MOUSE
AccessionPrimary (citable) accession number: P35428
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: July 9, 2014
This is version 129 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot