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Protein

Transcription factor HES-1

Gene

HES1

Organism
Homo sapiens (Human)
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. 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 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 transcription factor activity Source: UniProtKB
  8. 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
Complete GO annotation...

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: HPA
  3. nucleus Source: UniProtKB
Complete GO annotation...

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

BgeeiQ14469.
CleanExiHS_HES1.
ExpressionAtlasiQ14469. baseline and differential.
GenevestigatoriQ14469.

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 – 333Combined sources
Helixi40 – 6526Combined sources
Helixi71 – 733Combined sources
Helixi77 – 9317Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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.
GeneTreeiENSGT00700000104168.
HOGENOMiHOG000236346.
HOVERGENiHBG005960.
InParanoidiQ14469.
KOiK06054.
OMAiATPASMN.
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

        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
NAMTYPGQPH PALQAPPPPP PGPGGPQHAP FAPPPPLVPI PGGAAPPPGG
210 220 230 240 250
APCKLGSQAG EAAKVFGGFQ VVPAPDGQFA FLIPNGAFAH SGPVIPVYTS
260 270 280
NSGTSVGPNA VSPSSGPSLT ADSMWRPWRN
Length:280
Mass (Da):29,541
Last modified:November 1, 1996 - v1
Checksum:iF9342A88FC749E3C
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2MH3NMR-A/B27-95[»]
ProteinModelPortaliQ14469.
SMRiQ14469. Positions 27-95.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

PTM databases

PhosphoSiteiQ14469.

Polymorphism databases

DMDMi3913825.

Proteomic databases

MaxQBiQ14469.
PaxDbiQ14469.
PRIDEiQ14469.

Protocols and materials databases

DNASUi3280.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi3280.
GeneCardsiGC03P193853.
HGNCiHGNC:5192. HES1.
MIMi139605. gene.
neXtProtiNX_Q14469.
PharmGKBiPA29465.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG319418.
GeneTreeiENSGT00700000104168.
HOGENOMiHOG000236346.
HOVERGENiHBG005960.
InParanoidiQ14469.
KOiK06054.
OMAiATPASMN.
OrthoDBiEOG780RN7.
PhylomeDBiQ14469.
TreeFamiTF351373.

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.

Miscellaneous databases

GeneWikiiHES1.
GenomeRNAii3280.
NextBioi13023.
PROiQ14469.
SOURCEiSearch...

Gene expression databases

BgeeiQ14469.
CleanExiHS_HES1.
ExpressionAtlasiQ14469. baseline and differential.
GenevestigatoriQ14469.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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].
  8. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

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: March 4, 2015
This is version 142 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

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.