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Q14469

- HES1_HUMAN

UniProt

Q14469 - HES1_HUMAN

Protein

Transcription factor HES-1

Gene

HES1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 137 (01 Oct 2014)
      Sequence version 1 (01 Nov 1996)
      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. Binds DNA on N-box motifs: 5'-CACNAG-3' with high affinity and on E-box motifs: 5'-CANNTG-3' with low affinity By similarity. 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 similarity1 Publication

    GO - Molecular functioni

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

    GO - Biological processi

    1. adenohypophysis development Source: Ensembl
    2. artery morphogenesis Source: BHF-UCL
    3. ascending aorta morphogenesis Source: BHF-UCL
    4. auditory receptor cell fate determination Source: Ensembl
    5. cardiac neural crest cell development involved in outflow tract morphogenesis Source: BHF-UCL
    6. cell adhesion Source: Ensembl
    7. cell maturation Source: Ensembl
    8. cell migration Source: Ensembl
    9. cell morphogenesis involved in neuron differentiation Source: Ensembl
    10. cochlea development Source: Ensembl
    11. comma-shaped body morphogenesis Source: Ensembl
    12. common bile duct development Source: Ensembl
    13. embryonic heart tube morphogenesis Source: BHF-UCL
    14. endocrine pancreas development Source: Reactome
    15. forebrain radial glial cell differentiation Source: UniProtKB
    16. glomerulus vasculature development Source: Ensembl
    17. hindbrain morphogenesis Source: Ensembl
    18. labyrinthine layer blood vessel development Source: Ensembl
    19. lateral inhibition Source: Ensembl
    20. liver development Source: Ensembl
    21. lung development Source: Ensembl
    22. metanephric nephron tubule morphogenesis Source: Ensembl
    23. midbrain development Source: Ensembl
    24. midbrain-hindbrain boundary morphogenesis Source: Ensembl
    25. negative regulation of auditory receptor cell differentiation Source: Ensembl
    26. negative regulation of forebrain neuron differentiation Source: UniProtKB
    27. negative regulation of glial cell proliferation Source: UniProtKB
    28. negative regulation of oligodendrocyte differentiation Source: UniProtKB
    29. negative regulation of pancreatic A cell differentiation Source: Ensembl
    30. negative regulation of pro-B cell differentiation Source: UniProtKB
    31. negative regulation of stem cell differentiation Source: UniProtKB
    32. negative regulation of stomach neuroendocrine cell differentiation Source: Ensembl
    33. negative regulation of transcription, DNA-templated Source: BHF-UCL
    34. negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    35. nervous system development Source: ProtInc
    36. neuronal stem cell maintenance Source: UniProtKB
    37. Notch signaling pathway Source: UniProtKB
    38. oculomotor nerve development Source: Ensembl
    39. outflow tract morphogenesis Source: BHF-UCL
    40. pharyngeal arch artery morphogenesis Source: BHF-UCL
    41. positive regulation of astrocyte differentiation Source: UniProtKB
    42. positive regulation of BMP signaling pathway Source: Ensembl
    43. positive regulation of cell proliferation Source: BHF-UCL
    44. positive regulation of DNA binding Source: UniProtKB
    45. positive regulation of JAK-STAT cascade Source: UniProtKB
    46. positive regulation of mitotic cell cycle, embryonic Source: BHF-UCL
    47. positive regulation of Notch signaling pathway Source: Ensembl
    48. positive regulation of T cell proliferation Source: Ensembl
    49. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
    50. positive regulation of tyrosine phosphorylation of Stat3 protein Source: UniProtKB
    51. protein complex assembly Source: UniProtKB
    52. regulation of fat cell differentiation Source: Ensembl
    53. regulation of secondary heart field cardioblast proliferation Source: BHF-UCL
    54. regulation of timing of neuron differentiation Source: Ensembl
    55. renal interstitial fibroblast development Source: Ensembl
    56. smoothened signaling pathway Source: Ensembl
    57. somatic stem cell maintenance Source: Ensembl
    58. S-shaped body morphogenesis Source: Ensembl
    59. STAT protein import into nucleus Source: UniProtKB
    60. telencephalon development Source: Ensembl
    61. thymus development Source: BHF-UCL
    62. trochlear nerve development Source: Ensembl
    63. ureteric bud morphogenesis Source: Ensembl
    64. vascular smooth muscle cell development Source: BHF-UCL
    65. ventricular septum development Source: BHF-UCL
    66. 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_118780. NOTCH1 Intracellular Domain Regulates Transcription.
    REACT_13673. Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells.
    REACT_160243. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
    REACT_160254. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
    REACT_163910. NOTCH2 intracellular domain regulates transcription.
    SignaLinkiQ14469.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Transcription factor HES-1
    Alternative name(s):
    Class B basic helix-loop-helix protein 39
    Short name:
    bHLHb39
    Hairy and enhancer of split 1
    Hairy homolog
    Hairy-like protein
    Short name:
    hHL
    Gene namesi
    Name:HES1
    Synonyms:BHLHB39, HL, HRY
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 3

    Organism-specific databases

    HGNCiHGNC:5192. HES1.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: Ensembl
    2. nucleoplasm Source: Reactome
    3. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA29465.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 280280Transcription factor HES-1PRO_0000127202Add
    BLAST

    Proteomic databases

    MaxQBiQ14469.
    PaxDbiQ14469.
    PRIDEiQ14469.

    PTM databases

    PhosphoSiteiQ14469.

    Expressioni

    Gene expression databases

    ArrayExpressiQ14469.
    BgeeiQ14469.
    CleanExiHS_HES1.
    GenevestigatoriQ14469.

    Organism-specific databases

    HPAiHPA050504.

    Interactioni

    Subunit structurei

    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 By similarity. Interacts with SIRT1. Interacts with an FA complex, composed of FANCA, FANCF, FANCG and FANCL, but not of FANCC, nor FANCE.By similarity2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    SIRT1Q96EB64EBI-2832522,EBI-1802965

    Protein-protein interaction databases

    BioGridi109514. 34 interactions.
    IntActiQ14469. 16 interactions.
    MINTiMINT-6774152.
    STRINGi9606.ENSP00000232424.

    Structurei

    Secondary structure

    1
    280
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi31 – 333
    Helixi40 – 6526
    Helixi71 – 733
    Helixi77 – 9317

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2MH3NMR-A/B27-95[»]
    ProteinModelPortaliQ14469.
    SMRiQ14469. 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
    Motifi275 – 2784WRPW motif

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi156 – 24691Pro-richAdd
    BLAST
    Compositional biasi249 – 27325Ser/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.By similarity
    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.
    InParanoidiQ14469.
    KOiK06054.
    OMAiMPADMME.
    OrthoDBiEOG780RN7.
    PhylomeDBiQ14469.
    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.

    Q14469-1 [UniParc]FASTAAdd to Basket

    « Hide

    MPADIMEKNS SSPVAATPAS VNTTPDKPKT ASEHRKSSKP IMEKRRRARI    50
    NESLSQLKTL ILDALKKDSS RHSKLEKADI LEMTVKHLRN LQRAQMTAAL 100
    STDPSVLGKY RAGFSECMNE VTRFLSTCEG VNTEVRTRLL GHLANCMTQI 150
    NAMTYPGQPH PALQAPPPPP PGPGGPQHAP FAPPPPLVPI PGGAAPPPGG 200
    APCKLGSQAG EAAKVFGGFQ VVPAPDGQFA FLIPNGAFAH SGPVIPVYTS 250
    NSGTSVGPNA VSPSSGPSLT ADSMWRPWRN 280
    Length:280
    Mass (Da):29,541
    Last modified:November 1, 1996 - v1
    Checksum:iF9342A88FC749E3C
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L19314 Genomic DNA. Translation: AAA65220.1.
    AF264785 mRNA. Translation: AAF73060.1.
    AK000415 mRNA. Translation: BAA91149.1.
    CR541843 mRNA. Translation: CAG46641.1.
    CCDSiCCDS3305.1.
    PIRiA53027.
    RefSeqiNP_005515.1. NM_005524.3.
    UniGeneiHs.250666.

    Genome annotation databases

    EnsembliENST00000232424; ENSP00000232424; ENSG00000114315.
    GeneIDi3280.
    KEGGihsa:3280.
    UCSCiuc003ftq.2. human.

    Polymorphism databases

    DMDMi3913825.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L19314 Genomic DNA. Translation: AAA65220.1 .
    AF264785 mRNA. Translation: AAF73060.1 .
    AK000415 mRNA. Translation: BAA91149.1 .
    CR541843 mRNA. Translation: CAG46641.1 .
    CCDSi CCDS3305.1.
    PIRi A53027.
    RefSeqi NP_005515.1. NM_005524.3.
    UniGenei Hs.250666.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2MH3 NMR - A/B 27-95 [» ]
    ProteinModelPortali Q14469.
    SMRi Q14469. Positions 27-95.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109514. 34 interactions.
    IntActi Q14469. 16 interactions.
    MINTi MINT-6774152.
    STRINGi 9606.ENSP00000232424.

    PTM databases

    PhosphoSitei Q14469.

    Polymorphism databases

    DMDMi 3913825.

    Proteomic databases

    MaxQBi Q14469.
    PaxDbi Q14469.
    PRIDEi Q14469.

    Protocols and materials databases

    DNASUi 3280.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000232424 ; ENSP00000232424 ; ENSG00000114315 .
    GeneIDi 3280.
    KEGGi hsa:3280.
    UCSCi uc003ftq.2. human.

    Organism-specific databases

    CTDi 3280.
    GeneCardsi GC03P193853.
    HGNCi HGNC:5192. HES1.
    HPAi HPA050504.
    MIMi 139605. gene.
    neXtProti NX_Q14469.
    PharmGKBi PA29465.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG319418.
    HOGENOMi HOG000236346.
    HOVERGENi HBG005960.
    InParanoidi Q14469.
    KOi K06054.
    OMAi MPADMME.
    OrthoDBi EOG780RN7.
    PhylomeDBi Q14469.
    TreeFami TF351373.

    Enzyme and pathway databases

    Reactomei REACT_118780. NOTCH1 Intracellular Domain Regulates Transcription.
    REACT_13673. Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells.
    REACT_160243. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
    REACT_160254. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
    REACT_163910. NOTCH2 intracellular domain regulates transcription.
    SignaLinki Q14469.

    Miscellaneous databases

    GeneWikii HES1.
    GenomeRNAii 3280.
    NextBioi 13023.
    PROi Q14469.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q14469.
    Bgeei Q14469.
    CleanExi HS_HES1.
    Genevestigatori Q14469.

    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. "Genomic cloning and chromosomal localization of HRY, the human homolog to the Drosophila segmentation gene, hairy."
      Feder J.N., Li L., Jan L.Y., Jan Y.-N.
      Genomics 20:56-61(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    2. "Functional analysis of human HRY in Drosophila."
      Yao J., Yeung S., Sun H., Chen N.
      Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Kidney.
    3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    4. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
      Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
      Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    5. "Human Sir2-related protein SIRT1 associates with the bHLH repressors HES1 and HEY2 and is involved in HES1- and HEY2-mediated transcriptional repression."
      Takata T., Ishikawa F.
      Biochem. Biophys. Res. Commun. 301:250-257(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SIRT1.
    6. "HES1 is a novel interactor of the Fanconi anemia core complex."
      Tremblay C.S., Huang F.F., Habi O., Huard C.C., Godin C., Levesque G., Carreau M.
      Blood 112:2062-2070(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH FA COMPLEX.
    7. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
      Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
      Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

    Entry informationi

    Entry nameiHES1_HUMAN
    AccessioniPrimary (citable) accession number: Q14469
    Secondary accession number(s): Q6FHB2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 15, 1998
    Last sequence update: November 1, 1996
    Last modified: October 1, 2014
    This is version 137 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 3
      Human chromosome 3: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3