Hey2 hairy/enhancer-of-split related with YRPW motif 2 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Hey2provided by MGI
Official Full Name: hairy/enhancer-of-split related with YRPW motif 2provided by MGI
Primary source: MGI:MGI:1341884
See related: Ensembl:ENSMUSG00000019789 AllianceGenome:MGI:1341884
Gene type: protein coding
RefSeq status: PROVISIONAL
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: CHF1; Hrt2; Herp1; hesr2; bHLHb32
Summary: Enables DNA-binding transcription repressor activity, RNA polymerase II-specific; cis-regulatory region sequence-specific DNA binding activity; and identical protein binding activity. Involved in several processes, including circulatory system development; mesenchymal cell development; and regulation of gene expression. Acts upstream of or within several processes, including cardiac muscle hypertrophy in response to stress; circulatory system development; and negative regulation of cardiac muscle cell apoptotic process. Located in cytoplasm and nucleus. Is expressed in several structures, including cardiovascular system; genitourinary system; nervous system; sensory organ; and tooth. Used to study aortic valve disease and tetralogy of Fallot. Orthologous to human HEY2 (hes related family bHLH transcription factor with YRPW motif 2). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Biased expression in ovary adult (RPKM 30.7), frontal lobe adult (RPKM 5.4) and 12 other tissues See more
Orthologs: human all
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Genomic context

Location:: 10 A4; 10 17.19 cM

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	10	NC_000076.7 (30708355..30718779, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	10	NC_000076.6 (30832359..30842783, complement)

Chromosome 10 - NC_000076.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Loss of myocardial Hey2/Hrt2 function disrupts rightward shift of atrioventricular cushion tissue and causes tricuspid atresia.
Title: Loss of myocardial Hey2/Hrt2 function disrupts rightward shift of atrioventricular cushion tissue and causes tricuspid atresia.
Genetic lineage tracing in skin reveals predominant expression of HEY2 in dermal papilla during telogen and that HEY2[+] cells contribute to the regeneration of dermal cells during wound healing.
Title: Genetic lineage tracing in skin reveals predominant expression of HEY2 in dermal papilla during telogen and that HEY2(+) cells contribute to the regeneration of dermal cells during wound healing.
Hey2 enhancer activity defines unipotent progenitors for left ventricular cardiomyocytes in juxta-cardiac field of early mouse embryo.
Title: Hey2 enhancer activity defines unipotent progenitors for left ventricular cardiomyocytes in juxta-cardiac field of early mouse embryo.
HIF-2alpha Inhibits Ameloblast Differentiation via Hey2 in Tooth Development.
Title: HIF-2α Inhibits Ameloblast Differentiation via Hey2 in Tooth Development.
A role of Hey2 transcription factor for right ventricle development through regulation of Tbx2-Mycn pathway during cardiac morphogenesis.
Title: A role of Hey2 transcription factor for right ventricle development through regulation of Tbx2-Mycn pathway during cardiac morphogenesis.
Expression of Hey2 transcription factor in the early embryonic ventricles is controlled through a distal enhancer by Tbx20 and Gata transcription factors.
Title: Expression of Hey2 transcription factor in the early embryonic ventricles is controlled through a distal enhancer by Tbx20 and Gata transcription factors.
Authors found that Hey2 is expressed in the endocardial cells of the atrioventricular canal and the outflow tract, as well as at the base of trabeculae, in addition to the reported expression in the ventricular compact myocardium.
Title: Notch signaling regulates Hey2 expression in a spatiotemporal dependent manner during cardiac morphogenesis and trabecular specification.
miR98 reduced the production of Abeta and improved oxidative stress and mitochondrial dysfunction through activation of the Notch signaling pathway by binding to HEY2 in Alzheimer's disease mice.
Title: MicroRNA-98 reduces amyloid β-protein production and improves oxidative stress and mitochondrial dysfunction through the Notch signaling pathway via HEY2 in Alzheimer's disease mice.
We also highlighted that Hey2 is involved in radiation-induced EndoMT and that Hey2 invalidation reduces EndoMT and tissue damage.
Title: Endothelial Hey2 deletion reduces endothelial-to-mesenchymal transition and mitigates radiation proctitis in mice.
Data implied that Hey2 function is restricted to transient amplifying cells of the ameloblast cell lineage and that Hey1 plays a role in the composition of the subodontoblastic layer, in addition to ameloblast differentiation.
Title: Hey1 and Hey2 are differently expressed during mouse tooth development.

Submit: New GeneRIF Correction See all GeneRIFs (41)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (3) 1 citation
Targeted (8) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:484888

Hey2 (e-PCR), detects polymorphism
- UniSTS:545947

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables DNA binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity	ISO Inferred from Sequence Orthology more info
enables DNA-binding transcription factor activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	ISO Inferred from Sequence Orthology more info
enables DNA-binding transcription repressor activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables RNA polymerase II-specific DNA-binding transcription factor binding	IEA Inferred from Electronic Annotation more info
enables RNA polymerase II-specific DNA-binding transcription factor binding	ISO Inferred from Sequence Orthology more info
enables cis-regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables histone deacetylase binding	IEA Inferred from Electronic Annotation more info
enables histone deacetylase binding	ISO Inferred from Sequence Orthology more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein dimerization activity	IEA Inferred from Electronic Annotation more info
enables sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables sequence-specific DNA binding	ISO Inferred from Sequence Orthology more info
enables sequence-specific double-stranded DNA binding	ISO Inferred from Sequence Orthology more info
enables transcription factor binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in Notch signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in Notch signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in Notch signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in Notch signaling pathway	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within anterior/posterior axis specification	IGI Inferred from Genetic Interaction more info	PubMed
involved_in anterior/posterior pattern specification	IBA Inferred from Biological aspect of Ancestor more info
involved_in aortic valve morphogenesis	IDA Inferred from Direct Assay more info	PubMed
involved_in arterial endothelial cell differentiation	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within artery development	IGI Inferred from Genetic Interaction more info	PubMed
involved_in ascending aorta morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in atrial septum morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within atrioventricular valve development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within blood vessel development	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within blood vessel endothelial cell differentiation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in cardiac epithelial to mesenchymal transition	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cardiac left ventricle morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of cardiac muscle cell apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of cardiac muscle cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cardiac muscle hypertrophy	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cardiac muscle hypertrophy in response to stress	IDA Inferred from Direct Assay more info	PubMed
involved_in cardiac right ventricle morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cardiac septum morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cardiac vascular smooth muscle cell development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cardiac ventricle morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cell fate commitment	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in circulatory system development	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within cochlea development	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within cochlea development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within coronary vasculature morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in dorsal aorta morphogenesis	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within endocardial cushion to mesenchymal transition involved in heart valve formation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in heart trabecula formation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in labyrinthine layer blood vessel development	IGI Inferred from Genetic Interaction more info	PubMed
involved_in mesenchymal cell development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in muscular septum morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of DNA-templated transcription	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of Notch signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of Notch signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of biomineral tissue development	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within negative regulation of cardiac muscle cell apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cardiac vascular smooth muscle cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cardiac vascular smooth muscle cell differentiation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of smooth muscle cell differentiation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within negative regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within negative regulation of transcription by RNA polymerase II	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of transcription initiation by RNA polymerase II	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of transcription initiation by RNA polymerase II	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of transcription regulatory region DNA binding	ISO Inferred from Sequence Orthology more info
involved_in outflow tract morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within pattern specification process	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within pattern specification process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of cardiac muscle cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of heart rate	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within protein-DNA complex assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in pulmonary artery morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in pulmonary valve morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of inner ear auditory receptor cell differentiation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in regulation of neurogenesis	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in regulation of vasculogenesis	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within tricuspid valve formation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in tricuspid valve morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in umbilical cord morphogenesis	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within vasculogenesis	IGI Inferred from Genetic Interaction more info	PubMed
involved_in ventricular cardiac muscle cell development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ventricular septum morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within ventricular trabecula myocardium morphogenesis	IGI Inferred from Genetic Interaction more info	PubMed

Component	Evidence Code	Pubs
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
part_of transcription regulator complex	ISS Inferred from Sequence or Structural Similarity more info	PubMed
part_of transcription repressor complex	IEA Inferred from Electronic Annotation more info
part_of transcription repressor complex	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: hairy/enhancer-of-split related with YRPW motif protein 2

Names: HES-related repressor protein 2; HESR-2; HRT-2; Hairy-E(spl)-related with YRPW motif 2; hairy and enhancer of split related 2; hairy and enhancer of split-related protein 2; hairy-related transcription factor 2; mHRT2; protein gridlock homolog

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_013904.1 → NP_038932.1 hairy/enhancer-of-split related with YRPW motif protein 2

See identical proteins and their annotated locations for NP_038932.1

Status: PROVISIONAL

Source sequence(s)

AF172287

Consensus CDS

CCDS23766.1

UniProtKB/Swiss-Prot

Q3TZ99, Q8CD44, Q9QUS4

UniProtKB/TrEMBL

Q0VGJ1

Related

ENSMUSP00000019924.9, ENSMUST00000019924.9

Conserved Domains (2) summary

smart00511
Location:120 → 165

ORANGE; Orange domain

cd00083
Location:49 → 105

HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...