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FLASH GENE

Symbol

HES1

contributors: mct/npt/pgu - updated : 04-04-2016

HGNC name	hairy and enhancer of split 1, (Drosophila)
HGNC id	5192

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

widely

expressed in

(based on citations)

organ(s)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive liver       predominantly   stomach       moderately Endocrine neuroendocrine pituitary     moderately   parathyroid       highly Lymphoid/Immune thymus       highly Nervous brain       highly   nerve       moderately Reproductive male system prostate     highly Respiratory lung       highly Urinary kidney         Visual eye       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Lymphoid

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic erythroid Homo sapiens Adult

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
	FRS2 regulates ERK levels to control a self-renewal target HES1 and proliferation of FGF-responsive neural stem/progenitor cells
	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
	DMRTA2 function is linked to the regulation of HES1 and other proneural genes, as demonstrated by genome-wide RNA-seq and direct binding of DMRTA2 to the HES1 genomic locus
	link between DMRTA2 modulation of HES1 expression and the maintenance of NPCs during cortical development

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
	System Type Disorder Pubmed osteoarticular bone ostéoporosis 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