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P35428

- HES1_MOUSE

UniProt

P35428 - HES1_MOUSE

Protein

Transcription factor HES-1

Gene

Hes1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 131 (01 Oct 2014)
      Sequence version 1 (01 Jun 1994)
      Previous versions | rss
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    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 binding Source: UniProtKB
    4. protein homodimerization activity Source: UniProtKB
    5. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription Source: UniProtKB
    6. sequence-specific DNA binding Source: UniProtKB
    7. sequence-specific DNA binding RNA polymerase II transcription factor activity Source: MGI
    8. sequence-specific DNA binding transcription factor activity Source: UniProtKB
    9. 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

    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

    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

    ArrayExpressiP35428.
    BgeeiP35428.
    CleanExiMM_HES1.
    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

    MPADIMEKNS SSPVAATPAS VNTTPDKPKT ASEHRKSSKP IMEKRRRARI    50
    NESLSQLKTL ILDALKKDSS RHSKLEKADI LEMTVKHLRN LQRAQMTAAL 100
    STDPSVLGKY RAGFSECMNE VTRFLSTCEG VNTEVRTRLL GHLANCMTQI 150
    NAMTYPGQAH PALQAPPPPP PSGPAGPQHA PFAPPPPPLV PIPGGAAPPP 200
    GSAPCKLGSQ AGEAAKVFGG FQVVPAPDGQ FAFLIPNGAF AHSGPVIPVY 250
    TSNSGTSVGP NAVSPSSGSS LTSDSMWRPW RN 282
    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

    ArrayExpressi P35428.
    Bgeei P35428.
    CleanExi MM_HES1.
    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

    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 1, 2014
    This is version 131 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