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Protein

Transcription factor HES-1

Gene

HES1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

GO - Biological processi

Keywordsi

Molecular functionDNA-binding, Repressor
Biological processTranscription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-210744 Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells
R-HSA-2122947 NOTCH1 Intracellular Domain Regulates Transcription
R-HSA-2197563 NOTCH2 intracellular domain regulates transcription
R-HSA-2644606 Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-2894862 Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-8940973 RUNX2 regulates osteoblast differentiation
R-HSA-8941856 RUNX3 regulates NOTCH signaling
R-HSA-9013508 NOTCH3 Intracellular Domain Regulates Transcription
SignaLinkiQ14469
SIGNORiQ14469

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
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000114315.3
HGNCiHGNC:5192 HES1
MIMi139605 gene
neXtProtiNX_Q14469

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi3280
OpenTargetsiENSG00000114315
PharmGKBiPA29465

Chemistry databases

ChEMBLiCHEMBL3734643

Polymorphism and mutation databases

BioMutaiHES1
DMDMi3913825

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001272021 – 280Transcription factor HES-1Add BLAST280

Proteomic databases

EPDiQ14469
MaxQBiQ14469
PaxDbiQ14469
PeptideAtlasiQ14469
PRIDEiQ14469
ProteomicsDBi60000

PTM databases

iPTMnetiQ14469
PhosphoSitePlusiQ14469

Expressioni

Gene expression databases

BgeeiENSG00000114315
CleanExiHS_HES1
GenevisibleiQ14469 HS

Organism-specific databases

HPAiHPA066929

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

GO - Molecular functioni

  • chaperone binding Source: Ensembl
  • histone deacetylase binding Source: BHF-UCL
  • protein homodimerization activity Source: UniProtKB
  • transcription factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi109514, 35 interactors
CORUMiQ14469
ELMiQ14469
IntActiQ14469, 16 interactors
MINTiQ14469
STRINGi9606.ENSP00000232424

Structurei

Secondary structure

1280
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi31 – 33Combined sources3
Helixi40 – 65Combined sources26
Helixi71 – 73Combined sources3
Helixi77 – 93Combined sources17

3D structure databases

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

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini34 – 91bHLHPROSITE-ProRule annotationAdd BLAST58
Domaini110 – 143OrangePROSITE-ProRule annotationAdd BLAST34

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi275 – 278WRPW motif4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi156 – 246Pro-richAdd BLAST91
Compositional biasi249 – 273Ser/Thr-richAdd BLAST25

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

Phylogenomic databases

eggNOGiKOG4304 Eukaryota
ENOG4111F0X LUCA
GeneTreeiENSGT00700000104168
HOGENOMiHOG000236346
HOVERGENiHBG005960
InParanoidiQ14469
KOiK06054
OMAiATPASMN
OrthoDBiEOG091G0GBN
PhylomeDBiQ14469
TreeFamiTF351373

Family and domain databases

CDDicd00083 HLH, 1 hit
Gene3Di4.10.280.10, 1 hit
InterProiView protein in InterPro
IPR011598 bHLH_dom
IPR036638 HLH_DNA-bd_sf
IPR003650 Orange_dom
PfamiView protein in Pfam
PF07527 Hairy_orange, 1 hit
PF00010 HLH, 1 hit
SMARTiView protein in SMART
SM00353 HLH, 1 hit
SM00511 ORANGE, 1 hit
SUPFAMiSSF47459 SSF47459, 1 hit
PROSITEiView protein in PROSITE
PS50888 BHLH, 1 hit
PS51054 ORANGE, 1 hit

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.3 human

Similar proteinsi

Entry informationi

Entry nameiHES1_HUMAN
AccessioniPrimary (citable) accession number: Q14469
Secondary accession number(s): Q6FHB2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: November 1, 1996
Last modified: June 20, 2018
This is version 172 of the entry and version 1 of the sequence. See 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

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