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transcription factor HES-1; class B basic helix-loop-helix protein 39; bHLHb39; Hairy & enhancer of split 1; Hairy homolog; Hairy-like protein; hHL (HES1, BHLHB39, HL, HRY)
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 & ASH1
- binds DNA on N-box motifs: 5'-CACNAG-3' with high affinity & on E-box motifs: 5'-CANNTG-3' with low affinity (putative)
- may play a role in a functional FA core complex response to DNA cross-link damage, being required for the stability & nuclear localization of FA core complex proteins, as well as for FANCD2 monoubiquitination in response to DNA damage
- transcription repression requires formation of a complex with a corepressor protein of the groucho/TLE family
- interacts (via WPRW motif) with TLE1, & more weakly with TLE2
- interacts with HES6 (putative)
- interacts with SIRT1
- interacts with an FA complex, composed of FANCA, FANCF, FANCG & FANCL, but not of FANCC, nor FANCE
- gene is downstream target of notch signalling
Structure:
- 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 (putative)
- the bHLH, as well as cooperation between the central Orange domain & the C-terminal WRPW motif, is required for transcriptional repressor activity (putative)
- contains 1 basic helix-loop-helix (bHLH) domain
- contains 1 Orange domain
Compartment: nucleus
General
phosphoprotein
transcriptional silencer (transcriptional repressor)
Properties
SIZE: entity length = 280 aa
MW = 30 kD
COMPARTMENT: cell nucleus
MOTIF: Ser phosphorylation site {S10}
Thr phosphorylation site {T24}
DNA-binding motif
SITE: 35-47
helix-loop-helix
NAME: helix-loop-helix
SITE: 48-92
FOR-BINDING-VIA: helix-loop-helix
Orange {110-143}
proline-rich region
SITE: 156-246
MOTIF: proline residue (SEVERAL)
threonine-rich region {249-273}
MOTIF: threonine residue (SEVERAL)
WRPW {275-278}
Database Correlations
OMIM 139605
UniProt Q14469
PFAM correlations
Entrez Gene 3280
Kegg hsa:3280
References
- UniProt :accession Q14469
- Entrez Gene :accession 3280