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P35428

- HES1_MOUSE

UniProt

P35428 - HES1_MOUSE

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Protein

Transcription factor HES-1

Gene

Hes1

Organism
Mus musculus (Mouse)
Status
Reviewed - 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

  1. DNA binding Source: MGI
  2. N-box binding Source: UniProtKB
  3. protein homodimerization activity Source: UniProtKB
  4. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription Source: UniProtKB
  5. sequence-specific DNA binding Source: UniProtKB
  6. sequence-specific DNA binding RNA polymerase II transcription factor activity Source: MGI
  7. sequence-specific DNA binding transcription factor activity Source: UniProtKB
  8. transcription factor binding Source: UniProtKB

GO - Biological processi

  1. adenohypophysis development Source: MGI
  2. aorta morphogenesis Source: BHF-UCL
  3. artery morphogenesis Source: BHF-UCL
  4. ascending aorta morphogenesis Source: BHF-UCL
  5. auditory receptor cell differentiation Source: MGI
  6. auditory receptor cell fate determination Source: MGI
  7. cardiac neural crest cell development involved in outflow tract morphogenesis Source: MGI
  8. cell adhesion Source: MGI
  9. cell fate commitment Source: MGI
  10. cell maturation Source: MGI
  11. cell migration Source: MGI
  12. cell morphogenesis involved in neuron differentiation Source: MGI
  13. cochlea development Source: MGI
  14. comma-shaped body morphogenesis Source: UniProtKB
  15. common bile duct development Source: MGI
  16. embryonic heart tube morphogenesis Source: BHF-UCL
  17. endocrine pancreas development Source: Reactome
  18. forebrain radial glial cell differentiation Source: UniProtKB
  19. glomerulus vasculature development Source: UniProtKB
  20. hindbrain morphogenesis Source: MGI
  21. in utero embryonic development Source: MGI
  22. labyrinthine layer blood vessel development Source: BHF-UCL
  23. lateral inhibition Source: MGI
  24. liver development Source: MGI
  25. lung development Source: MGI
  26. metanephric nephron tubule morphogenesis Source: UniProtKB
  27. midbrain development Source: MGI
  28. midbrain-hindbrain boundary morphogenesis Source: MGI
  29. negative regulation of auditory receptor cell differentiation Source: MGI
  30. negative regulation of cell differentiation Source: MGI
  31. negative regulation of forebrain neuron differentiation Source: UniProtKB
  32. negative regulation of glial cell proliferation Source: UniProtKB
  33. negative regulation of inner ear receptor cell differentiation Source: UniProtKB
  34. negative regulation of neuron differentiation Source: MGI
  35. negative regulation of oligodendrocyte differentiation Source: UniProtKB
  36. negative regulation of pancreatic A cell differentiation Source: MGI
  37. negative regulation of pro-B cell differentiation Source: UniProtKB
  38. negative regulation of stem cell differentiation Source: Ensembl
  39. negative regulation of stomach neuroendocrine cell differentiation Source: MGI
  40. negative regulation of transcription, DNA-templated Source: UniProtKB
  41. negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  42. neural tube development Source: MGI
  43. neuronal stem cell maintenance Source: UniProtKB
  44. Notch signaling pathway Source: UniProtKB
  45. oculomotor nerve development Source: MGI
  46. outflow tract morphogenesis Source: BHF-UCL
  47. pancreas development Source: MGI
  48. pattern specification process Source: MGI
  49. pharyngeal arch artery morphogenesis Source: BHF-UCL
  50. pituitary gland development Source: MGI
  51. positive regulation of astrocyte differentiation Source: UniProtKB
  52. positive regulation of BMP signaling pathway Source: MGI
  53. positive regulation of cell proliferation Source: BHF-UCL
  54. positive regulation of DNA binding Source: UniProtKB
  55. positive regulation of JAK-STAT cascade Source: UniProtKB
  56. positive regulation of mitotic cell cycle, embryonic Source: BHF-UCL
  57. positive regulation of Notch signaling pathway Source: UniProtKB
  58. positive regulation of T cell proliferation Source: MGI
  59. positive regulation of transcription, DNA-templated Source: UniProtKB
  60. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  61. positive regulation of tyrosine phosphorylation of Stat3 protein Source: UniProtKB
  62. protein complex assembly Source: UniProtKB
  63. regulation of fat cell differentiation Source: MGI
  64. regulation of neurogenesis Source: MGI
  65. regulation of secondary heart field cardioblast proliferation Source: MGI
  66. regulation of timing of cell differentiation Source: MGI
  67. regulation of timing of neuron differentiation Source: MGI
  68. regulation of transcription from RNA polymerase II promoter Source: MGI
  69. renal interstitial fibroblast development Source: UniProtKB
  70. smoothened signaling pathway Source: MGI
  71. somatic stem cell maintenance Source: MGI
  72. S-shaped body morphogenesis Source: UniProtKB
  73. STAT protein import into nucleus Source: UniProtKB
  74. telencephalon development Source: MGI
  75. thymus development Source: BHF-UCL
  76. transcription from RNA polymerase II promoter Source: GOC
  77. trochlear nerve development Source: MGI
  78. ureteric bud morphogenesis Source: UniProtKB
  79. vascular smooth muscle cell development Source: BHF-UCL
  80. ventricular septum development Source: BHF-UCL
  81. 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_196464. NOTCH1 Intracellular Domain Regulates Transcription.
REACT_196593. NOTCH2 intracellular domain regulates transcription.
REACT_222486. 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: Chromosome 16

Organism-specific databases

MGIiMGI:104853. Hes1.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: MGI
  2. intracellular Source: MGI
  3. nucleoplasm Source: Reactome
  4. 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.
GenevestigatoriP35428.

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.

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.
OMAiMPADMME.
OrthoDBiEOG780RN7.
PhylomeDBiP35428.
TreeFamiTF351373.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
IPR003650. Orange.
IPR018352. Orange_subgr.
[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:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
Links Updated
D16464 Genomic DNA. Translation: BAA03931.1 .
BC018375 mRNA. Translation: AAH18375.1 .
BC051428 mRNA. Translation: AAH51428.1 .
CCDSi CCDS28098.1.
PIRi A53336.
RefSeqi NP_032261.1. NM_008235.2.
UniGenei Mm.390859.

3D structure databases

ProteinModelPortali P35428.
SMRi P35428. Positions 27-95.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 200275. 5 interactions.

Chemistry

ChEMBLi CHEMBL1075292.

PTM databases

PhosphoSitei P35428.

Proteomic databases

PRIDEi P35428.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000023171 ; ENSMUSP00000023171 ; ENSMUSG00000022528 .
GeneIDi 15205.
KEGGi mmu:15205.
UCSCi uc007ywl.1. mouse.

Organism-specific databases

CTDi 3280.
MGIi MGI:104853. Hes1.

Phylogenomic databases

eggNOGi NOG319418.
HOGENOMi HOG000236346.
HOVERGENi HBG005960.
InParanoidi P35428.
KOi K06054.
OMAi MPADMME.
OrthoDBi EOG780RN7.
PhylomeDBi P35428.
TreeFami TF351373.

Enzyme and pathway databases

Reactomei REACT_196464. NOTCH1 Intracellular Domain Regulates Transcription.
REACT_196593. NOTCH2 intracellular domain regulates transcription.
REACT_222486. Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells.

Miscellaneous databases

NextBioi 287757.
PROi P35428.
SOURCEi Search...

Gene expression databases

Bgeei P35428.
CleanExi MM_HES1.
ExpressionAtlasi P35428. baseline and differential.
Genevestigatori P35428.

Family and domain databases

Gene3Di 4.10.280.10. 1 hit.
InterProi IPR011598. bHLH_dom.
IPR003650. Orange.
IPR018352. Orange_subgr.
[Graphical view ]
Pfami PF07527. Hairy_orange. 1 hit.
PF00010. HLH. 1 hit.
[Graphical view ]
SMARTi SM00353. HLH. 1 hit.
SM00511. ORANGE. 1 hit.
[Graphical view ]
SUPFAMi SSF47459. SSF47459. 1 hit.
PROSITEi PS50888. BHLH. 1 hit.
PS51054. ORANGE. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: October 29, 2014
This is version 132 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