Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol HES1 contributors: mct/npt/pgu - updated : 04-04-2014
HGNC name hairy and enhancer of split 1, (Drosophila)
HGNC id 5192
Location 3q29      Physical location : 193.853.933 - 193.856.396
Synonym name
  • transcription factor HES-1
  • hairy homolog
  • protein GT335
  • protein KNP-I
  • hairy-like
  • Synonym symbol(s) HRY, HHL, bHLHb39, HES-1, FLJ20408, EVI128, KNPI, HL
    DNA
    TYPE functioning gene
    STRUCTURE 2.46 kb     4 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    FGF12 3q29-qter fibroblast growth factor 12 LOC151963 3q29 similar to BcDNA:GH11415 gene product LOC285388 3q29 similar to vascular endothelial zinc finger 1 HRASLS 3q28-q29 HRAS-like suppressor DKFZp761I1011 3q29 hypothetical protein DKFZp761I1011 OPA1 3q28-q29 optic atrophy 1 (autosomal dominant) LOC389186 3 LOC389186 HES1 3q28-q29 hairy and enhancer of split 1, (Drosophila) LOC254808 3q29 hypothetical protein LOC254808 LOC285280 3q29 similar to Carboxypeptidase N 83 kDa chain (Carboxypeptidase N regulatory subunit) LRRC15 3q29 leucine rich repeat containing 15 GP5 3q29 glycoprotein V (platelet) AFURS1 3q29 ATPase family homolog up-regulated in senescence cells LOC391605 3 similar to 60S ribosomal protein L23a LOC93109 3q29 hypothetical protein BC007772 FLJ11301 3q29 hypothetical protein FLJ11301 FLJ90022 3q29 hypothetical protein FLJ90022 LOC285303 3q29 similar to MGC27169 protein FLJ35155 3q29 hypothetical protein FLJ35155 CENTB2 3q29 centaurin, beta 2 PPP1R2 3q29 protein phosphatase 1, regulatory (inhibitor) subunit 2 LOC391606 3 similar to ribosomal protein L24 LOC255812 3q29 hypothetical protein LOC255812 LOC389187 3 LOC389187 MUC20 3q29 mucin 20 MUC4 3q29 mucin 4, tracheobronchial LOC285253 3q29 similar to SPBPJ4664.02 ACK1 3q29 activated Cdc42-associated kinase 1 LOC391607 3 hypothetical gene supported by AJ271448; NM_174907 LOC375386 3q29 similar to Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial precursor (Fp) (Flavoprotein subunit of complex II) LOC391608 3 hypothetical gene supported by AJ271448; NM_174907 TFRC 3q29 transferrin receptor (p90, CD71)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 1471 29.4 280 - 2009 19321451
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   predominantly
     stomach   moderately
    Endocrineneuroendocrinepituitary  moderately
     parathyroid   highly
    Lymphoid/Immunethymus   highly
    Nervousbrain   highly
     nerve   moderately
    Reproductivemale systemprostate  highly
    Respiratorylung   highly
    Urinarykidney    
    Visualeye   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticerythroid Homo sapiensAdult
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, fetal
    Text
  • moderately in umbilical cord
  • in the developing central nervous system, highly expressed by neural stem cells )
  • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a bHLH domain required for both DNA binding and dimerization with other bHLH factors
  • an Orange domain involved in protein-protein interactions
  • a particular type of basic domain that contains a helix interrupting protein that binds to the N-box rather than the canonical E-box
  • a WRPW motif at the C terminus involved in protein-protein interactions
  • HOMOLOGY
    interspecies homolog to rattus Hes1 (98.2 pc)
    homolog to murine Hes1 (98.2 pc)
    Homologene
    FAMILY
  • basic helix-loop-helix family of transcription factors
  • ES1 family
  • CATEGORY adhesion , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    basic FUNCTION
  • an immediate early response gene to growth factor
  • transcriptional repressor of genes that require a bHLH protein for their transcription
  • at later stages of development, promote gliogenesis
  • play an essential role in neural development by regulating proliferation, differentiation and specification of neural stem cells
  • may act as a negative regulator of myogenesis by inhibiting the functions of MYOD1 and ASCL1
  • involved in reversible cell cycle exit both during normal cellular quiescence and pathologically in the setting of tumorigenesis
  • being a novel interacting protein of the Fanconi anemia core complex
  • important overlapping functions of HES1 and PROP1 in cell differentiation and movement that are critical for pituitary organogenesis
  • plays an essential role in the development of many organs by promoting the maintenance of stem/progenitor cells, by controlling the reversibility of cellular quiescence, and by regulating both cell fate decisions and the timing of several developmental events
  • negatively regulates expression of downstream target genes and antagonizes the effects of bHLH activators
  • cyclic gene contributing to heterogeneous responses of embryonic stem cells even under the same environmental conditions
  • with HES5 are dispensable for cartilage and endochondral bone formation
  • transcription factor that regulates osteoblastogenesis
  • by inhibiting osteoblast function and inducing bone resorption, HES1 is an intracellular determinant of bone mass and structure
  • modulates bone remodeling, as perturbing its expression in osteoblastic cells results in significant alterations in cancellous bone volume and microarchitecture
  • plays a role in regulating the location and density of mesencephalic dopaminergic neurons
  • plays an important role in synaptic function in differentiated neurons
  • in primary hepatocellular carcinoma, HES1 protein expression inversely correlates with CDKN1C/P57 mRNA levels
  • important regulator of hematopoiesis
  • information provided by HES1/HEY1 downstream of NOTCH1 as well as myogenic regulatory factors (MRFs) activities are integrated at the level of the CDKN1C enhancer to regulate the decision between progenitor cell maintenance and muscle differentiation
  • mediates tumor suppressive roles of Notch signaling in AML development, probably by downregulating FLT3 expression
  • CELLULAR PROCESS cell life, differentiation
    cell life, proliferation/growth
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS development
    text liver, nervous system, pituitary gland and lung development
  • negative regulation of auditory receptor cell differentiation
  • negative regulation of neuron differentiation
  • positive regulation of cell proliferation
  • regulation of timing of cell differentiation
  • PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA binding
    RNA
    small molecule
    protein
  • HEY2 interacts genetically with HES1 for early embryonic development and survival
  • interacting with FAAP100 (contributes to transcriptional regulation of HES1-responsive genes, including HES1 and CDKN1A)
  • HES6 is an inhibitor of HES1 during neuronal development
  • interaction of HES1 and PARP1 in B-ALL modulates the function of the HES1 transcriptional complex and signals through PARP1 to induce apoptosis
  • NFIA also downregulates the activity of the NOTCH signaling pathway via repression of the key NOTCH effector HES1
  • PTF1A-induced DLL1 expression stimulates multipotent pancreatic progenitor cells (MPCs) proliferation and pancreatic growth by maintaining HES1 expression and PTF1A protein levels
  • CDKN1C is a target of transcriptional repression by the NOTCH effector, HES1
  • EZH2 is required for the transient repression of HES1 in erythroid cells
  • GATA1 utilizes IKAROS and polycomb repressive complex 2 to suppress HES1 and to promote erythropoiesis
  • ADAM10-dependent regulation of DLL1 and DLL4 expression in association with changes in HES1 and HEY1 expression
  • HES1 directly bound to the promoter region of the FMS-like tyrosine kinase 3 (FLT3) gene and downregulated the promoter activity
  • cell & other
    REGULATION
    Phosphorylated by could be regulated by c-Jun N-terminal kinase MAPK8, that directly phosphorylates HES1 at Ser-263
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • may represent a biomarker for prediction of patients with poor prognosis in hepatocellular carcinoma
  • Therapy target
    SystemTypeDisorderPubmed
    osteoarticularboneostéoporosis
    targeted down-regulation of Hes1 expression or activity in osteoblasts could be considered as a possible strategy in the development of novel therapies for osteoporosis
    ANIMAL & CELL MODELS
  • Hes1 homozygous null mutant mice displayed a neural tube closure defect, and exencephaly was induced at the mid/hindbrain boundary