Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q14469 (HES1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:HES1
Synonyms:BHLHB39, HL, HRY
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length280 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.6

Subunit structure

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. Ref.5 Ref.6

Subcellular location

Nucleus.

Domain

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 similarities

Contains 1 bHLH (basic helix-loop-helix) domain.

Contains 1 Orange domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   LigandDNA-binding
   Molecular functionRepressor
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processNotch signaling pathway

Inferred from direct assay PubMed 16160079. Source: UniProtKB

S-shaped body morphogenesis

Inferred from electronic annotation. Source: Ensembl

STAT protein import into nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

adenohypophysis development

Inferred from electronic annotation. Source: Ensembl

artery morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

ascending aorta morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

auditory receptor cell fate determination

Inferred from electronic annotation. Source: Ensembl

cardiac neural crest cell development involved in outflow tract morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

cell adhesion

Inferred from electronic annotation. Source: Ensembl

cell maturation

Inferred from electronic annotation. Source: Ensembl

cell migration

Inferred from electronic annotation. Source: Ensembl

cell morphogenesis involved in neuron differentiation

Inferred from electronic annotation. Source: Ensembl

cochlea development

Inferred from electronic annotation. Source: Ensembl

comma-shaped body morphogenesis

Inferred from electronic annotation. Source: Ensembl

common bile duct development

Inferred from electronic annotation. Source: Ensembl

embryonic heart tube morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

endocrine pancreas development

Traceable author statement. Source: Reactome

forebrain radial glial cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

glomerulus vasculature development

Inferred from electronic annotation. Source: Ensembl

hindbrain morphogenesis

Inferred from electronic annotation. Source: Ensembl

labyrinthine layer blood vessel development

Inferred from electronic annotation. Source: Ensembl

lateral inhibition

Inferred from electronic annotation. Source: Ensembl

liver development

Inferred from electronic annotation. Source: Ensembl

lung development

Inferred from electronic annotation. Source: Ensembl

metanephric nephron tubule morphogenesis

Inferred from electronic annotation. Source: Ensembl

midbrain development

Inferred from electronic annotation. Source: Ensembl

midbrain-hindbrain boundary morphogenesis

Inferred from electronic annotation. Source: Ensembl

negative regulation of auditory receptor cell differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of forebrain neuron differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of glial cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of oligodendrocyte differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of pancreatic A cell differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of pro-B cell differentiation

Inferred from mutant phenotype PubMed 12032823. Source: UniProtKB

negative regulation of stem cell differentiation

Inferred from mutant phenotype PubMed 19682396. Source: UniProtKB

negative regulation of stomach neuroendocrine cell differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 12032823. Source: UniProtKB

negative regulation of transcription, DNA-templated

Inferred from direct assay Ref.5. Source: BHF-UCL

nervous system development

Traceable author statement Ref.1. Source: ProtInc

neuronal stem cell maintenance

Inferred from expression pattern PubMed 19682396. Source: UniProtKB

oculomotor nerve development

Inferred from electronic annotation. Source: Ensembl

outflow tract morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

pharyngeal system development

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of BMP signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of DNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of JAK-STAT cascade

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of Notch signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of T cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of astrocyte differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell proliferation

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of mitotic cell cycle, embryonic

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of tyrosine phosphorylation of Stat3 protein

Inferred from sequence or structural similarity. Source: UniProtKB

protein complex assembly

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of fat cell differentiation

Inferred from electronic annotation. Source: Ensembl

regulation of secondary heart field cardioblast proliferation

Inferred from sequence or structural similarity. Source: BHF-UCL

regulation of timing of neuron differentiation

Inferred from electronic annotation. Source: Ensembl

renal interstitial cell development

Inferred from electronic annotation. Source: Ensembl

smoothened signaling pathway

Inferred from electronic annotation. Source: Ensembl

somatic stem cell maintenance

Inferred from electronic annotation. Source: Ensembl

telencephalon development

Inferred from electronic annotation. Source: Ensembl

thymus development

Inferred from sequence or structural similarity. Source: BHF-UCL

trochlear nerve development

Inferred from electronic annotation. Source: Ensembl

ureteric bud morphogenesis

Inferred from electronic annotation. Source: Ensembl

vascular smooth muscle cell development

Inferred from sequence or structural similarity. Source: BHF-UCL

ventricular septum development

Inferred from sequence or structural similarity. Source: BHF-UCL

ventricular septum morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: Ensembl

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionDNA binding

Traceable author statement PubMed 7906273. Source: ProtInc

N-box binding

Inferred from sequence or structural similarity. Source: UniProtKB

RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription

Inferred from sequence or structural similarity. Source: UniProtKB

histone deacetylase binding

Inferred from physical interaction Ref.5. Source: BHF-UCL

protein homodimerization activity

Inferred from sequence or structural similarity. Source: UniProtKB

sequence-specific DNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 17681138. Source: UniProtKB

transcription factor binding

Non-traceable author statement PubMed 17611704. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

SIRT1Q96EB64EBI-2832522,EBI-1802965

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 280280Transcription factor HES-1
PRO_0000127202

Regions

Domain34 – 9158bHLH
Domain110 – 14334Orange
Motif275 – 2784WRPW motif
Compositional bias156 – 24691Pro-rich
Compositional bias249 – 27325Ser/Thr-rich

Sequences

Sequence LengthMass (Da)Tools
Q14469 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: F9342A88FC749E3C

FASTA28029,541
        10         20         30         40         50         60 
MPADIMEKNS SSPVAATPAS VNTTPDKPKT ASEHRKSSKP IMEKRRRARI NESLSQLKTL 

        70         80         90        100        110        120 
ILDALKKDSS RHSKLEKADI LEMTVKHLRN LQRAQMTAAL STDPSVLGKY RAGFSECMNE 

       130        140        150        160        170        180 
VTRFLSTCEG VNTEVRTRLL GHLANCMTQI NAMTYPGQPH PALQAPPPPP PGPGGPQHAP 

       190        200        210        220        230        240 
FAPPPPLVPI PGGAAPPPGG APCKLGSQAG EAAKVFGGFQ VVPAPDGQFA FLIPNGAFAH 

       250        260        270        280 
SGPVIPVYTS NSGTSVGPNA VSPSSGPSLT ADSMWRPWRN 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L19314 Genomic DNA. Translation: AAA65220.1.
AF264785 mRNA. Translation: AAF73060.1.
AK000415 mRNA. Translation: BAA91149.1.
CR541843 mRNA. Translation: CAG46641.1.
PIRA53027.
RefSeqNP_005515.1. NM_005524.3.
UniGeneHs.250666.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2MH3NMR-A/B27-95[»]
ProteinModelPortalQ14469.
SMRQ14469. Positions 47-95, 102-150.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109514. 34 interactions.
IntActQ14469. 16 interactions.
MINTMINT-6774152.
STRING9606.ENSP00000232424.

PTM databases

PhosphoSiteQ14469.

Polymorphism databases

DMDM3913825.

Proteomic databases

PaxDbQ14469.
PRIDEQ14469.

Protocols and materials databases

DNASU3280.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000232424; ENSP00000232424; ENSG00000114315.
GeneID3280.
KEGGhsa:3280.
UCSCuc003ftq.2. human.

Organism-specific databases

CTD3280.
GeneCardsGC03P193853.
HGNCHGNC:5192. HES1.
HPAHPA050504.
MIM139605. gene.
neXtProtNX_Q14469.
PharmGKBPA29465.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG319418.
HOGENOMHOG000236346.
HOVERGENHBG005960.
InParanoidQ14469.
KOK06054.
OMAMPADMME.
OrthoDBEOG780RN7.
PhylomeDBQ14469.
TreeFamTF351373.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_116125. Disease.
SignaLinkQ14469.

Gene expression databases

ArrayExpressQ14469.
BgeeQ14469.
CleanExHS_HES1.
GenevestigatorQ14469.

Family and domain databases

Gene3D4.10.280.10. 1 hit.
InterProIPR011598. bHLH_dom.
IPR003650. Orange.
IPR018352. Orange_subgr.
[Graphical view]
PfamPF07527. Hairy_orange. 1 hit.
PF00010. HLH. 1 hit.
[Graphical view]
SMARTSM00353. HLH. 1 hit.
SM00511. ORANGE. 1 hit.
[Graphical view]
SUPFAMSSF47459. SSF47459. 1 hit.
PROSITEPS50888. BHLH. 1 hit.
PS51054. ORANGE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiHES1.
GenomeRNAi3280.
NextBio13023.
PROQ14469.
SOURCESearch...

Entry information

Entry nameHES1_HUMAN
AccessionPrimary (citable) accession number: Q14469
Secondary accession number(s): Q6FHB2
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: November 1, 1996
Last modified: April 16, 2014
This is version 132 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM