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HEY2 hes related family bHLH transcription factor with YRPW motif 2 [ Homo sapiens (human) ]

Gene ID: 23493, updated on 2-Oct-2018

Summary

Official Symbol
HEY2provided by HGNC
Official Full Name
hes related family bHLH transcription factor with YRPW motif 2provided by HGNC
Primary source
HGNC:HGNC:4881
See related
Ensembl:ENSG00000135547 MIM:604674; Vega:OTTHUMG00000015512
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
GRL; CHF1; HRT2; HERP1; HESR2; bHLHb32; GRIDLOCK
Summary
This gene encodes a member of the hairy and enhancer of split-related (HESR) family of basic helix-loop-helix (bHLH)-type transcription factors. The encoded protein forms homo- or hetero-dimers that localize to the nucleus and interact with a histone deacetylase complex to repress transcription. Expression of this gene is induced by the Notch signal transduction pathway. Two similar and redundant genes in mouse are required for embryonic cardiovascular development, and are also implicated in neurogenesis and somitogenesis. Alternatively spliced transcript variants have been found, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]
Expression
Broad expression in endometrium (RPKM 2.9), brain (RPKM 2.7) and 22 other tissues See more
Orthologs

Genomic context

See HEY2 in Genome Data Viewer
Location:
6q22.31
Exon count:
7
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 6 NC_000006.12 (125747639..125762243)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (126066211..126082415)

Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC102723341 Neighboring gene uncharacterized LOC105377986 Neighboring gene long intergenic non-protein coding RNA 2523 Neighboring gene transfer RNA-Glu (CTC) 1-7 Neighboring gene NCOA7 antisense RNA 1 Neighboring gene nuclear receptor coactivator 7

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

Description
Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death.
NHGRI GWA Catalog

Pathways from BioSystems

  • Breast cancer, organism-specific biosystem (from KEGG)
    Breast cancer, organism-specific biosystemBreast cancer is the leading cause of cancer death among women worldwide. The vast majority of breast cancers are carcinomas that originate from cells lining the milk-forming ducts of the mammary gla...
  • Breast cancer, conserved biosystem (from KEGG)
    Breast cancer, conserved biosystemBreast cancer is the leading cause of cancer death among women worldwide. The vast majority of breast cancers are carcinomas that originate from cells lining the milk-forming ducts of the mammary gla...
  • Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants, organism-specific biosystem (from REACTOME)
    Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants, organism-specific biosystemWhen found in cis, HD and PEST domain mutations act synergistically, increasing NOTCH1 transcriptional activity up to ~40-fold, compared with up to ~10-fold and up to ~2-fold increase with HD mutatio...
  • Constitutive Signaling by NOTCH1 PEST Domain Mutants, organism-specific biosystem (from REACTOME)
    Constitutive Signaling by NOTCH1 PEST Domain Mutants, organism-specific biosystemAs NOTCH1 PEST domain is intracellular, NOTCH1 PEST domain mutants are expected to behave as the wild-type NOTCH1 with respect to ligand binding and proteolytic cleavage mediated activation of signal...
  • Disease, organism-specific biosystem (from REACTOME)
    Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
  • Diseases of signal transduction, organism-specific biosystem (from REACTOME)
    Diseases of signal transduction, organism-specific biosystemSignaling processes are central to human physiology (e.g., Pires-da Silva & Sommer 2003), and their disruption by either germ-line and somatic mutation can lead to serious disease. Here, the molecula...
  • Heart Development, organism-specific biosystem (from WikiPathways)
    Heart Development, organism-specific biosystemThis pathway has been largely adapted from an article by Deepak Srivastava, Cell. 2006 Sep 22;126(6):1037-48. In this pathway are known transcription factors, miRNAs and regulatory proteins that impa...
  • NOTCH1 Intracellular Domain Regulates Transcription, organism-specific biosystem (from REACTOME)
    NOTCH1 Intracellular Domain Regulates Transcription, organism-specific biosystemNICD1 produced by activation of NOTCH1 in response to Delta and Jagged ligands (DLL/JAG) presented in trans, traffics to the nucleus where it acts as a transcription regulator. In the nucleus, NICD1 ...
  • Neural Crest Differentiation, organism-specific biosystem (from WikiPathways)
    Neural Crest Differentiation, organism-specific biosystemGene regulatory network model of cranial neural crest cell (CNCC) development, adaped from PMID: 19575671. Most interactions in the model are proposed to regulate transcription of core factors involv...
  • Notch Signaling Pathway, organism-specific biosystem (from WikiPathways)
    Notch Signaling Pathway, organism-specific biosystemThe Notch pathway is an evolutionally conserved signaling pathway which plays an important role in diverse developmental and physiological processes. These include cell-fate determination, tissue pat...
  • Notch-mediated HES/HEY network, organism-specific biosystem (from Pathway Interaction Database)
    Notch-mediated HES/HEY network, organism-specific biosystem
    Notch-mediated HES/HEY network
  • Signal Transduction, organism-specific biosystem (from REACTOME)
    Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
  • Signaling by NOTCH, organism-specific biosystem (from REACTOME)
    Signaling by NOTCH, organism-specific biosystemThe Notch Signaling Pathway (NSP) is a highly conserved pathway for cell-cell communication. NSP is involved in the regulation of cellular differentiation, proliferation, and specification. For exam...
  • Signaling by NOTCH1, organism-specific biosystem (from REACTOME)
    Signaling by NOTCH1, organism-specific biosystemNOTCH1 functions as both a transmembrane receptor presented on the cell surface and as a transcriptional regulator in the nucleus.NOTCH1 receptor presented on the plasma membrane is activated by a me...
  • Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer, organism-specific biosystem (from REACTOME)
    Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer, organism-specific biosystemMutations in the heterodimerization domain (HD) and PEST domain of NOTCH1 are frequently found in cis in T-cell acute lymphoblastic leukemia. While HD mutations alone result in up to ~10-fold increas...
  • Signaling by NOTCH1 PEST Domain Mutants in Cancer, organism-specific biosystem (from REACTOME)
    Signaling by NOTCH1 PEST Domain Mutants in Cancer, organism-specific biosystemNOTCH1 PEST domain mutations are frequently found in T-cell acute lymphoblastic leukemia (T-ALL). PEST domain mutations interfere with ubiquitination-mediated NOTCH1 downregulation and result in prol...
  • Signaling by NOTCH1 in Cancer, organism-specific biosystem (from REACTOME)
    Signaling by NOTCH1 in Cancer, organism-specific biosystemHuman NOTCH1 was cloned as a chromosome 9 gene, translocated to the T-cell beta receptor (TCBR) promoter on chromosome 7 in T-cell acute lymphoblastic leukemia (T-ALL) (Ellisen et al. 1991). This tra...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • MGC10720

Gene Ontology Provided by GOA

Function Evidence Code Pubs
DNA-binding transcription factor activity IDA
Inferred from Direct Assay
more info
PubMed 
DNA-binding transcription factor activity, RNA polymerase II-specific IDA
Inferred from Direct Assay
more info
PubMed 
DNA-binding transcription factor activity, RNA polymerase II-specific ISA
Inferred from Sequence Alignment
more info
 
DNA-binding transcription factor activity, RNA polymerase II-specific ISM
Inferred from Sequence Model
more info
PubMed 
DNA-binding transcription factor activity, RNA polymerase II-specific NAS
Non-traceable Author Statement
more info
PubMed 
RNA polymerase II activating transcription factor binding IPI
Inferred from Physical Interaction
more info
PubMed 
RNA polymerase II regulatory region sequence-specific DNA binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
histone deacetylase binding IPI
Inferred from Physical Interaction
more info
PubMed 
microsatellite binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
microsatellite binding IDA
Inferred from Direct Assay
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein heterodimerization activity IEA
Inferred from Electronic Annotation
more info
 
protein homodimerization activity IEA
Inferred from Electronic Annotation
more info
 
proximal promoter DNA-binding transcription activator activity, RNA polymerase II-specific IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
proximal promoter DNA-binding transcription repressor activity, RNA polymerase II-specific IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
sequence-specific DNA binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
sequence-specific DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
sequence-specific double-stranded DNA binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
transcription corepressor activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
transcription factor activity, RNA polymerase II core promoter sequence-specific DNA binding ISS
Inferred from Sequence or Structural Similarity
more info
 
transcription factor binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
transcription factor binding NAS
Non-traceable Author Statement
more info
PubMed 
Process Evidence Code Pubs
Notch signaling involved in heart development IC
Inferred by Curator
more info
PubMed 
Notch signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
Notch signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
 
anterior/posterior axis specification IEA
Inferred from Electronic Annotation
more info
 
arterial endothelial cell differentiation ISS
Inferred from Sequence or Structural Similarity
more info
 
ascending aorta morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
atrial septum morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
blood vessel development IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cardiac epithelial to mesenchymal transition ISS
Inferred from Sequence or Structural Similarity
more info
 
cardiac epithelial to mesenchymal transition TAS
Traceable Author Statement
more info
PubMed 
cardiac left ventricle morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
cardiac muscle hypertrophy in response to stress IEA
Inferred from Electronic Annotation
more info
 
cardiac right ventricle morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
cardiac septum morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
cardiac vascular smooth muscle cell development IEA
Inferred from Electronic Annotation
more info
 
cardiac ventricle morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
cell differentiation IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cell fate commitment IEA
Inferred from Electronic Annotation
more info
 
cochlea development IEA
Inferred from Electronic Annotation
more info
 
coronary vasculature morphogenesis IEA
Inferred from Electronic Annotation
more info
 
dorsal aorta morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
endocardial cushion to mesenchymal transition involved in heart valve formation IEA
Inferred from Electronic Annotation
more info
 
heart development IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
heart trabecula formation IEA
Inferred from Electronic Annotation
more info
 
labyrinthine layer blood vessel development ISS
Inferred from Sequence or Structural Similarity
more info
 
mesenchymal cell development ISS
Inferred from Sequence or Structural Similarity
more info
 
muscular septum morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of Notch signaling pathway IEA
Inferred from Electronic Annotation
more info
 
negative regulation of cardiac muscle cell apoptotic process IEA
Inferred from Electronic Annotation
more info
 
negative regulation of cardiac vascular smooth muscle cell differentiation ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of gene expression ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of transcription by RNA polymerase II IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of transcription by transcription factor localization ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of transcription from RNA polymerase II promoter involved in smooth muscle cell differentiation ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of transcription initiation from RNA polymerase II promoter IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of transcription regulatory region DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of transcription, DNA-templated IDA
Inferred from Direct Assay
more info
PubMed 
outflow tract morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of cardiac muscle cell proliferation IEA
Inferred from Electronic Annotation
more info
 
positive regulation of heart rate IEA
Inferred from Electronic Annotation
more info
 
positive regulation of transcription by RNA polymerase II IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of transcription by RNA polymerase II ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of transcription, DNA-templated TAS
Traceable Author Statement
more info
 
protein-DNA complex assembly IEA
Inferred from Electronic Annotation
more info
 
pulmonary artery morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
pulmonary valve morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of inner ear auditory receptor cell differentiation IEA
Inferred from Electronic Annotation
more info
 
regulation of neurogenesis IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
regulation of vasculogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
smooth muscle cell differentiation NAS
Non-traceable Author Statement
more info
PubMed 
tricuspid valve formation IEA
Inferred from Electronic Annotation
more info
 
tricuspid valve morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
umbilical cord morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
vascular smooth muscle cell development IEP
Inferred from Expression Pattern
more info
PubMed 
vasculogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
ventricular cardiac muscle cell development ISS
Inferred from Sequence or Structural Similarity
more info
 
ventricular septum morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
ventricular trabecula myocardium morphogenesis IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
colocalizes_with Sin3 complex IDA
Inferred from Direct Assay
more info
PubMed 
cytoplasm ISS
Inferred from Sequence or Structural Similarity
more info
 
nucleoplasm TAS
Traceable Author Statement
more info
 
nucleus IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
nucleus ISS
Inferred from Sequence or Structural Similarity
more info
 
transcriptional repressor complex IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

Preferred Names
hairy/enhancer-of-split related with YRPW motif protein 2
Names
HES-related repressor protein 1
HES-related repressor protein 2
HESR-2
HRT-2
cardiovascular basic helix-loop-helix factor 1
cardiovascular helix-loop-helix factor 1
class B basic helix-loop-helix protein 32
hCHF1
hHRT2
hairy and enhancer of split-related protein 2
hairy-related transcription factor 2
hairy/enhancer-of-split related with YRPW motif 2
protein gridlock homolog

NCBI Reference Sequences (RefSeq)

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)

  1. NM_012259.2NP_036391.1  hairy/enhancer-of-split related with YRPW motif protein 2

    See identical proteins and their annotated locations for NP_036391.1

    Status: REVIEWED

    Source sequence(s)
    AJ249545, BC007707, BI549391
    Consensus CDS
    CCDS5131.1
    UniProtKB/Swiss-Prot
    Q9UBP5
    Related
    ENSP00000357348.3, OTTHUMP00000017138, ENST00000368364.3, OTTHUMT00000042077
    Conserved Domains (2) summary
    smart00511
    Location:119165
    ORANGE; Orange domain
    cd00083
    Location:49105
    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, ...

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000006.12 Reference GRCh38.p12 Primary Assembly

    Range
    125747639..125762243
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017010629.2XP_016866118.1  hairy/enhancer-of-split related with YRPW motif protein 2 isoform X1

    UniProtKB/TrEMBL
    Q5TF93
    Related
    ENSP00000357349.1, OTTHUMP00000017139, ENST00000368365.5
    Conserved Domains (2) summary
    smart00511
    Location:73119
    ORANGE; Orange domain
    cd00083
    Location:359
    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, ...
  2. XM_017010628.1XP_016866117.1  hairy/enhancer-of-split related with YRPW motif protein 2 isoform X1

    UniProtKB/TrEMBL
    Q5TF93
    Conserved Domains (2) summary
    smart00511
    Location:73119
    ORANGE; Orange domain
    cd00083
    Location:359
    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, ...
  3. XM_017010627.1XP_016866116.1  hairy/enhancer-of-split related with YRPW motif protein 2 isoform X1

    UniProtKB/TrEMBL
    Q5TF93
    Conserved Domains (2) summary
    smart00511
    Location:73119
    ORANGE; Orange domain
    cd00083
    Location:359
    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, ...
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