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Protein

Transcription factor HES-1

Gene

Hes1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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
  • DNA binding transcription factor activity Source: UniProtKB
  • histone deacetylase binding Source: MGI
  • N-box binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: MGI
  • sequence-specific DNA binding Source: UniProtKB
  • transcriptional repressor activity, RNA polymerase II proximal promoter sequence-specific DNA binding 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 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
  • establishment of epithelial cell polarity Source: MGI
  • forebrain radial glial cell differentiation Source: UniProtKB
  • glomerulus vasculature development Source: UniProtKB
  • hindbrain morphogenesis Source: MGI
  • inner ear auditory receptor cell differentiation Source: MGI
  • inner ear receptor cell stereocilium organization 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 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 auditory receptor cell differentiation Source: MGI
  • 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 by RNA polymerase II Source: UniProtKB
  • neural tube development Source: MGI
  • neuronal stem cell population maintenance Source: UniProtKB
  • Notch signaling pathway Source: MGI
  • 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 by RNA polymerase II Source: BHF-UCL
  • positive regulation of tyrosine phosphorylation of STAT protein Source: UniProtKB
  • protein-containing complex assembly Source: UniProtKB
  • regulation of epithelial cell proliferation Source: MGI
  • regulation of fat cell differentiation Source: MGI
  • regulation of inner ear auditory receptor 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 by RNA polymerase II Source: MGI
  • renal interstitial fibroblast development Source: UniProtKB
  • smoothened signaling pathway Source: MGI
  • somatic stem cell population 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, DNA-templated Source: UniProtKB-KW
  • 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

Keywordsi

Molecular functionDNA-binding, Repressor
Biological processTranscription, Transcription regulation

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 16

Organism-specific databases

MGIiMGI:104853 Hes1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL1075292

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001272031 – 282Transcription factor HES-1Add BLAST282

Proteomic databases

PaxDbiP35428
PeptideAtlasiP35428
PRIDEiP35428

PTM databases

iPTMnetiP35428
PhosphoSitePlusiP35428

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

BgeeiENSMUSG00000022528
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

GO - Molecular functioni

  • chaperone binding Source: MGI
  • histone deacetylase binding Source: MGI
  • protein homodimerization activity Source: UniProtKB
  • transcription factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi200275, 5 interactors
ELMiP35428
STRINGi10090.ENSMUSP00000023171

Chemistry databases

BindingDBiP35428

Structurei

3D structure databases

ProteinModelPortaliP35428
SMRiP35428
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini34 – 91bHLHPROSITE-ProRule annotationAdd BLAST58
Domaini110 – 143OrangePROSITE-ProRule annotationAdd BLAST34

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi277 – 280WRPW motif4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi156 – 248Pro-richAdd BLAST93
Compositional biasi251 – 273Ser/Thr-richAdd BLAST23

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

Phylogenomic databases

eggNOGiKOG4304 Eukaryota
ENOG4111F0X LUCA
GeneTreeiENSGT00700000104168
HOGENOMiHOG000236346
HOVERGENiHBG005960
InParanoidiP35428
KOiK06054
OMAiATPASMN
OrthoDBiEOG091G0GBN
PhylomeDBiP35428
TreeFamiTF351373

Family and domain databases

CDDicd00083 HLH, 1 hit
Gene3Di4.10.280.10, 1 hit
InterProiView protein in InterPro
IPR011598 bHLH_dom
IPR036638 HLH_DNA-bd_sf
IPR003650 Orange_dom
PfamiView protein in Pfam
PF07527 Hairy_orange, 1 hit
PF00010 HLH, 1 hit
SMARTiView protein in SMART
SM00353 HLH, 1 hit
SM00511 ORANGE, 1 hit
SUPFAMiSSF47459 SSF47459, 1 hit
PROSITEiView protein in PROSITE
PS50888 BHLH, 1 hit
PS51054 ORANGE, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiHES1_MOUSE
AccessioniPrimary (citable) accession number: P35428
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: April 25, 2018
This is version 161 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health