Human Gene HEY2 (ENST00000368364.4_4) from GENCODE V47lift37
  Description: hes related family bHLH transcription factor with YRPW motif 2 (from RefSeq NM_012259.3)
Gencode Transcript: ENST00000368364.4_4
Gencode Gene: ENSG00000135547.9_7
Transcript (Including UTRs)
   Position: hg19 chr6:126,070,778-126,082,415 Size: 11,638 Total Exon Count: 5 Strand: +
Coding Region
   Position: hg19 chr6:126,070,923-126,080,948 Size: 10,026 Coding Exon Count: 5 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr6:126,070,778-126,082,415)mRNA (may differ from genome)Protein (337 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
HGNCMalacardsMGIOMIMPubMedReactome
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: HEY2_HUMAN
DESCRIPTION: RecName: Full=Hairy/enhancer-of-split related with YRPW motif protein 2; AltName: Full=Cardiovascular helix-loop-helix factor 1; Short=hCHF1; AltName: Full=Class B basic helix-loop-helix protein 32; Short=bHLHb32; AltName: Full=HES-related repressor protein 2; AltName: Full=Hairy and enhancer of split-related protein 2; Short=HESR-2; AltName: Full=Hairy-related transcription factor 2; Short=HRT-2; Short=hHRT2; AltName: Full=Protein gridlock homolog;
FUNCTION: Downstream effector of Notch signaling which may be required for cardiovascular development. Transcriptional repressor which binds preferentially to the canonical E box sequence 5'- CACGTG-3'. Represses transcription by the cardiac transcriptional activators GATA4 and GATA6.
SUBUNIT: May self-associate (By similarity). Interacts with GATA4, HES1 and HEYL (By similarity). Interacts with HDAC1, NCOR1 and SIN3A (By similarity). Interacts with ARNT and GATA6.
INTERACTION: Q96EB6:SIRT1; NbExp=3; IntAct=EBI-750630, EBI-1802965;
SUBCELLULAR LOCATION: Nucleus (By similarity).
SIMILARITY: Belongs to the HEY family.
SIMILARITY: Contains 1 bHLH (basic helix-loop-helix) domain.
SIMILARITY: Contains 1 Orange domain.

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: HEY2
Diseases sorted by gene-association score: tricuspid atresia (16), tricuspid valve stenosis (16), labyrinthitis (7), pediatric ependymoma (6), tetralogy of fallot (5), alagille syndrome 1 (5), tricuspid valve disease (5), brugada syndrome (3)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 45.83 RPKM in Artery - Tibial
Total median expression: 222.27 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -75.70145-0.522 Picture PostScript Text
3' UTR -345.901467-0.236 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR011598 - HLH_dom
IPR003650 - Orange
IPR018352 - Orange_subgr

Pfam Domains:
PF00010 - Helix-loop-helix DNA-binding domain
PF07527 - Hairy Orange

SCOP Domains:
158457 - Orange domain-like
47459 - HLH, helix-loop-helix DNA-binding domain
49842 - TNF-like

ModBase Predicted Comparative 3D Structure on Q9UBP5
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details Gene Details  
Gene SorterGene Sorter Gene Sorter  
 RGDEnsembl   
      
      

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding
GO:0000983 transcription factor activity, RNA polymerase II core promoter sequence-specific
GO:0000989 transcription factor activity, transcription factor binding
GO:0001102 RNA polymerase II activating transcription factor binding
GO:0003677 DNA binding
GO:0003700 transcription factor activity, sequence-specific DNA binding
GO:0005515 protein binding
GO:0008134 transcription factor binding
GO:0035939 microsatellite binding
GO:0042803 protein homodimerization activity
GO:0042826 histone deacetylase binding
GO:0043565 sequence-specific DNA binding
GO:0046982 protein heterodimerization activity
GO:0046983 protein dimerization activity

Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0001568 blood vessel development
GO:0001570 vasculogenesis
GO:0003150 muscular septum morphogenesis
GO:0003151 outflow tract morphogenesis
GO:0003171 atrioventricular valve development
GO:0003184 pulmonary valve morphogenesis
GO:0003186 tricuspid valve morphogenesis
GO:0003195 tricuspid valve formation
GO:0003199 endocardial cushion to mesenchymal transition involved in heart valve formation
GO:0003208 cardiac ventricle morphogenesis
GO:0003214 cardiac left ventricle morphogenesis
GO:0003215 cardiac right ventricle morphogenesis
GO:0003222 ventricular trabecula myocardium morphogenesis
GO:0003300 cardiac muscle hypertrophy
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0007219 Notch signaling pathway
GO:0007275 multicellular organism development
GO:0007389 pattern specification process
GO:0007507 heart development
GO:0009948 anterior/posterior axis specification
GO:0010460 positive regulation of heart rate
GO:0010468 regulation of gene expression
GO:0010621 negative regulation of transcription by transcription factor localization
GO:0010629 negative regulation of gene expression
GO:0010667 negative regulation of cardiac muscle cell apoptotic process
GO:0014031 mesenchymal cell development
GO:0014898 cardiac muscle hypertrophy in response to stress
GO:0035910 ascending aorta morphogenesis
GO:0035912 dorsal aorta morphogenesis
GO:0036304 umbilical cord morphogenesis
GO:0045165 cell fate commitment
GO:0045607 regulation of auditory receptor cell differentiation
GO:0045746 negative regulation of Notch signaling pathway
GO:0045892 negative regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0051145 smooth muscle cell differentiation
GO:0055015 ventricular cardiac muscle cell development
GO:0060045 positive regulation of cardiac muscle cell proliferation
GO:0060317 cardiac epithelial to mesenchymal transition
GO:0060347 heart trabecula formation
GO:0060411 cardiac septum morphogenesis
GO:0060412 ventricular septum morphogenesis
GO:0060413 atrial septum morphogenesis
GO:0060633 negative regulation of transcription initiation from RNA polymerase II promoter
GO:0060716 labyrinthine layer blood vessel development
GO:0060840 artery development
GO:0060842 arterial endothelial cell differentiation
GO:0060948 cardiac vascular smooth muscle cell development
GO:0060977 coronary vasculature morphogenesis
GO:0061156 pulmonary artery morphogenesis
GO:0061314 Notch signaling involved in heart development
GO:0065004 protein-DNA complex assembly
GO:0090102 cochlea development
GO:0097084 vascular smooth muscle cell development
GO:2000678 negative regulation of transcription regulatory region DNA binding
GO:2000723 negative regulation of cardiac vascular smooth muscle cell differentiation
GO:2000820 negative regulation of transcription from RNA polymerase II promoter involved in smooth muscle cell differentiation
GO:2001212 regulation of vasculogenesis

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0017053 transcriptional repressor complex
GO:0016580 Sin3 complex


-  Descriptions from all associated GenBank mRNAs
  AK303890 - Homo sapiens cDNA FLJ53591 complete cds, highly similar to Hairy/enhancer-of-split related with YRPW motif 2.
JB837399 - Sequence 10 from Patent WO2013106494.
JD590325 - Sequence 3 from Patent WO2015015498.
AF173901 - Homo sapiens basic helix-loop-helix factor 1 (CHF1) mRNA, complete cds.
AK289943 - Homo sapiens cDNA FLJ75594 complete cds, highly similar to Homo sapiens hairy/enhancer-of-split related with YRPW motif 2 (HEY2), mRNA.
AF232238 - Homo sapiens HES-related repressor protein 1 HERP1 mRNA, complete cds.
AB044755 - Homo sapiens Hey2 mRNA for basic-helix-loop-helix protein, complete cds.
BC007707 - Homo sapiens hairy/enhancer-of-split related with YRPW motif 2, mRNA (cDNA clone MGC:10720 IMAGE:3945225), complete cds.
AF237949 - Homo sapiens GRIDLOCK mRNA, complete cds.
AJ249545 - Homo sapiens mRNA for basic-helix-loop-helix protein, bHLH (Hey2 gene).
CU675765 - Synthetic construct Homo sapiens gateway clone IMAGE:100018996 5' read HEY2 mRNA.
AB463717 - Synthetic construct DNA, clone: pF1KB7665, Homo sapiens HEY2 gene for hairy/enhancer-of-split related with YRPW motif 2, without stop codon, in Flexi system.
BT020067 - Homo sapiens hairy/enhancer-of-split related with YRPW motif 2 mRNA, complete cds.
BT020068 - Homo sapiens hairy/enhancer-of-split related with YRPW motif 2 mRNA, complete cds.
KJ893387 - Synthetic construct Homo sapiens clone ccsbBroadEn_02781 HEY2 gene, encodes complete protein.
AF311884 - Homo sapiens hairy-related transcription factor 2 mRNA, complete cds.
JD430588 - Sequence 411612 from Patent EP1572962.
JD314280 - Sequence 295304 from Patent EP1572962.
JD337403 - Sequence 318427 from Patent EP1572962.
JD474878 - Sequence 455902 from Patent EP1572962.
JD095850 - Sequence 76874 from Patent EP1572962.
JD301955 - Sequence 282979 from Patent EP1572962.
JD471539 - Sequence 452563 from Patent EP1572962.
JD311365 - Sequence 292389 from Patent EP1572962.
JD094846 - Sequence 75870 from Patent EP1572962.
JD450439 - Sequence 431463 from Patent EP1572962.
JD298587 - Sequence 279611 from Patent EP1572962.
JD424559 - Sequence 405583 from Patent EP1572962.
JD314897 - Sequence 295921 from Patent EP1572962.
JD249505 - Sequence 230529 from Patent EP1572962.
JD315505 - Sequence 296529 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  BioCarta from NCI Cancer Genome Anatomy Project
h_hesPathway - Segmentation Clock

Reactome (by CSHL, EBI, and GO)

Protein Q9UBP5 (Reactome details) participates in the following event(s):

R-HSA-9008177 RUNX2 binds HEY1,HEY2,HES1
R-HSA-9013508 NOTCH3 Intracellular Domain Regulates Transcription
R-HSA-2122947 NOTCH1 Intracellular Domain Regulates Transcription
R-HSA-2644606 Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-2894862 Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-8940973 RUNX2 regulates osteoblast differentiation
R-HSA-9012852 Signaling by NOTCH3
R-HSA-1980143 Signaling by NOTCH1
R-HSA-2644602 Signaling by NOTCH1 PEST Domain Mutants in Cancer
R-HSA-2894858 Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer
R-HSA-8941326 RUNX2 regulates bone development
R-HSA-157118 Signaling by NOTCH
R-HSA-2644603 Signaling by NOTCH1 in Cancer
R-HSA-8878166 Transcriptional regulation by RUNX2
R-HSA-162582 Signal Transduction
R-HSA-5663202 Diseases of signal transduction
R-HSA-212436 Generic Transcription Pathway
R-HSA-1643685 Disease
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-74160 Gene expression (Transcription)

-  Other Names for This Gene
  Alternate Gene Symbols: BHLHB32, CHF1, ENST00000368364.1, ENST00000368364.2, ENST00000368364.3, GRL, HERP, HERP1, HEY2_HUMAN, HRT2, NM_012259, Q9UBP5, uc318grx.1, uc318grx.2
UCSC ID: ENST00000368364.4_4
RefSeq Accession: NM_012259.3
Protein: Q9UBP5 (aka HEY2_HUMAN)

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.