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Protein

Transcription factor HES-1

Gene

Hes1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity

GO - Molecular functioni

  • chaperone binding Source: MGI
  • DNA binding Source: MGI
  • histone deacetylase binding Source: MGI
  • N-box binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription Source: UniProtKB
  • sequence-specific DNA binding Source: UniProtKB
  • sequence-specific DNA binding RNA polymerase II transcription factor activity Source: MGI
  • sequence-specific DNA binding transcription factor activity Source: UniProtKB
  • transcription factor binding Source: UniProtKB

GO - Biological processi

  • adenohypophysis development Source: MGI
  • aorta morphogenesis Source: BHF-UCL
  • artery morphogenesis Source: BHF-UCL
  • ascending aorta morphogenesis Source: BHF-UCL
  • auditory receptor cell differentiation Source: MGI
  • auditory receptor cell fate determination Source: MGI
  • cardiac neural crest cell development involved in outflow tract morphogenesis Source: MGI
  • cell adhesion Source: MGI
  • cell fate commitment Source: MGI
  • cell maturation Source: MGI
  • cell migration Source: MGI
  • cell morphogenesis involved in neuron differentiation Source: MGI
  • cochlea development Source: MGI
  • comma-shaped body morphogenesis Source: UniProtKB
  • common bile duct development Source: MGI
  • embryonic heart tube morphogenesis Source: BHF-UCL
  • endocrine pancreas development Source: Reactome
  • forebrain radial glial cell differentiation Source: UniProtKB
  • glomerulus vasculature development Source: UniProtKB
  • hindbrain morphogenesis Source: MGI
  • in utero embryonic development Source: MGI
  • labyrinthine layer blood vessel development Source: BHF-UCL
  • lateral inhibition Source: MGI
  • liver development Source: MGI
  • lung development Source: MGI
  • metanephric nephron tubule morphogenesis Source: UniProtKB
  • midbrain development Source: MGI
  • midbrain-hindbrain boundary morphogenesis Source: MGI
  • negative regulation of auditory receptor cell differentiation Source: MGI
  • negative regulation of cell differentiation Source: MGI
  • negative regulation of forebrain neuron differentiation Source: UniProtKB
  • negative regulation of glial cell proliferation Source: UniProtKB
  • negative regulation of inner ear receptor cell differentiation Source: UniProtKB
  • negative regulation of neuron differentiation Source: MGI
  • negative regulation of oligodendrocyte differentiation Source: UniProtKB
  • negative regulation of pancreatic A cell differentiation Source: MGI
  • negative regulation of pro-B cell differentiation Source: UniProtKB
  • negative regulation of stem cell differentiation Source: MGI
  • negative regulation of stomach neuroendocrine cell differentiation Source: MGI
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • neural tube development Source: MGI
  • neuronal stem cell maintenance Source: UniProtKB
  • Notch signaling pathway Source: UniProtKB
  • oculomotor nerve development Source: MGI
  • outflow tract morphogenesis Source: BHF-UCL
  • pancreas development Source: MGI
  • pattern specification process Source: MGI
  • pharyngeal arch artery morphogenesis Source: BHF-UCL
  • pituitary gland development Source: MGI
  • positive regulation of astrocyte differentiation Source: UniProtKB
  • positive regulation of BMP signaling pathway Source: MGI
  • positive regulation of cell proliferation Source: BHF-UCL
  • positive regulation of DNA binding Source: UniProtKB
  • positive regulation of JAK-STAT cascade Source: UniProtKB
  • positive regulation of mitotic cell cycle, embryonic Source: BHF-UCL
  • positive regulation of Notch signaling pathway Source: UniProtKB
  • positive regulation of protein targeting to mitochondrion Source: MGI
  • positive regulation of T cell proliferation Source: MGI
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • positive regulation of tyrosine phosphorylation of Stat3 protein Source: UniProtKB
  • protein complex assembly Source: UniProtKB
  • regulation of fat cell differentiation Source: MGI
  • regulation of neurogenesis Source: MGI
  • regulation of secondary heart field cardioblast proliferation Source: MGI
  • regulation of timing of cell differentiation Source: MGI
  • regulation of timing of neuron differentiation Source: MGI
  • regulation of transcription from RNA polymerase II promoter Source: MGI
  • renal interstitial fibroblast development Source: UniProtKB
  • smoothened signaling pathway Source: MGI
  • somatic stem cell maintenance Source: MGI
  • S-shaped body morphogenesis Source: UniProtKB
  • STAT protein import into nucleus Source: UniProtKB
  • telencephalon development Source: MGI
  • thymus development Source: BHF-UCL
  • transcription from RNA polymerase II promoter Source: GOC
  • trochlear nerve development Source: MGI
  • ureteric bud morphogenesis Source: UniProtKB
  • vascular smooth muscle cell development Source: BHF-UCL
  • ventricular septum development Source: BHF-UCL
  • ventricular septum morphogenesis Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiREACT_278898. NOTCH2 intracellular domain regulates transcription.
REACT_334977. NOTCH1 Intracellular Domain Regulates Transcription.
REACT_346510. Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells.

Names & Taxonomyi

Protein namesi
Recommended name:
Transcription factor HES-1
Alternative name(s):
Hairy and enhancer of split 1
Gene namesi
Name:Hes1
Synonyms:Hes-1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 16

Organism-specific databases

MGIiMGI:104853. Hes1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: MGI
  • intracellular Source: MGI
  • nucleoplasm Source: MGI
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 282282Transcription factor HES-1PRO_0000127203Add
BLAST

Proteomic databases

PRIDEiP35428.

PTM databases

PhosphoSiteiP35428.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiP35428.
CleanExiMM_HES1.
ExpressionAtlasiP35428. baseline and differential.
GenevisibleiP35428. MM.

Interactioni

Subunit structurei

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).By similarity

Protein-protein interaction databases

BioGridi200275. 5 interactions.
STRINGi10090.ENSMUSP00000023171.

Structurei

3D structure databases

ProteinModelPortaliP35428.
SMRiP35428. Positions 27-95.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini34 – 9158bHLHPROSITE-ProRule annotationAdd
BLAST
Domaini110 – 14334OrangePROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi277 – 2804WRPW motif

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi156 – 24893Pro-richAdd
BLAST
Compositional biasi251 – 27323Ser/Thr-richAdd
BLAST

Domaini

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 similaritiesi

Contains 1 bHLH (basic helix-loop-helix) domain.PROSITE-ProRule annotation
Contains 1 Orange domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG319418.
HOGENOMiHOG000236346.
HOVERGENiHBG005960.
InParanoidiP35428.
KOiK06054.
OMAiATPASMN.
OrthoDBiEOG780RN7.
PhylomeDBiP35428.
TreeFamiTF351373.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
IPR003650. Orange.
[Graphical view]
PfamiPF07527. Hairy_orange. 1 hit.
PF00010. HLH. 1 hit.
[Graphical view]
SMARTiSM00353. HLH. 1 hit.
SM00511. ORANGE. 1 hit.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiPS50888. BHLH. 1 hit.
PS51054. ORANGE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P35428-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPADIMEKNS SSPVAATPAS VNTTPDKPKT ASEHRKSSKP IMEKRRRARI
60 70 80 90 100
NESLSQLKTL ILDALKKDSS RHSKLEKADI LEMTVKHLRN LQRAQMTAAL
110 120 130 140 150
STDPSVLGKY RAGFSECMNE VTRFLSTCEG VNTEVRTRLL GHLANCMTQI
160 170 180 190 200
NAMTYPGQAH PALQAPPPPP PSGPAGPQHA PFAPPPPPLV PIPGGAAPPP
210 220 230 240 250
GSAPCKLGSQ AGEAAKVFGG FQVVPAPDGQ FAFLIPNGAF AHSGPVIPVY
260 270 280
TSNSGTSVGP NAVSPSSGSS LTSDSMWRPW RN
Length:282
Mass (Da):29,749
Last modified:June 1, 1994 - v1
Checksum:i88C7700C5EF7DA26
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D16464 Genomic DNA. Translation: BAA03931.1.
BC018375 mRNA. Translation: AAH18375.1.
BC051428 mRNA. Translation: AAH51428.1.
CCDSiCCDS28098.1.
PIRiA53336.
RefSeqiNP_032261.1. NM_008235.2.
UniGeneiMm.390859.

Genome annotation databases

EnsembliENSMUST00000023171; ENSMUSP00000023171; ENSMUSG00000022528.
GeneIDi15205.
KEGGimmu:15205.
UCSCiuc007ywl.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D16464 Genomic DNA. Translation: BAA03931.1.
BC018375 mRNA. Translation: AAH18375.1.
BC051428 mRNA. Translation: AAH51428.1.
CCDSiCCDS28098.1.
PIRiA53336.
RefSeqiNP_032261.1. NM_008235.2.
UniGeneiMm.390859.

3D structure databases

ProteinModelPortaliP35428.
SMRiP35428. Positions 27-95.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200275. 5 interactions.
STRINGi10090.ENSMUSP00000023171.

Chemistry

BindingDBiP35428.
ChEMBLiCHEMBL1075292.

PTM databases

PhosphoSiteiP35428.

Proteomic databases

PRIDEiP35428.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000023171; ENSMUSP00000023171; ENSMUSG00000022528.
GeneIDi15205.
KEGGimmu:15205.
UCSCiuc007ywl.1. mouse.

Organism-specific databases

CTDi3280.
MGIiMGI:104853. Hes1.

Phylogenomic databases

eggNOGiNOG319418.
HOGENOMiHOG000236346.
HOVERGENiHBG005960.
InParanoidiP35428.
KOiK06054.
OMAiATPASMN.
OrthoDBiEOG780RN7.
PhylomeDBiP35428.
TreeFamiTF351373.

Enzyme and pathway databases

ReactomeiREACT_278898. NOTCH2 intracellular domain regulates transcription.
REACT_334977. NOTCH1 Intracellular Domain Regulates Transcription.
REACT_346510. Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells.

Miscellaneous databases

NextBioi287757.
PROiP35428.
SOURCEiSearch...

Gene expression databases

BgeeiP35428.
CleanExiMM_HES1.
ExpressionAtlasiP35428. baseline and differential.
GenevisibleiP35428. MM.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
IPR003650. Orange.
[Graphical view]
PfamiPF07527. Hairy_orange. 1 hit.
PF00010. HLH. 1 hit.
[Graphical view]
SMARTiSM00353. HLH. 1 hit.
SM00511. ORANGE. 1 hit.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiPS50888. BHLH. 1 hit.
PS51054. ORANGE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.

Entry informationi

Entry nameiHES1_MOUSE
AccessioniPrimary (citable) accession number: P35428
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: June 24, 2015
This is version 139 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.