HEY2
Hairy/enhancer-of-split related with YRPW motif protein 2
Also known as: bHLHb32, HERP1, HESR2, HEY2_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q9UBP5
- Gene
- HEY2
- Ensembl
- ENSG00000135547
- Chromosome
- 6
- Canonical length
- 337 aa
- Protein class
- Predicted intracellular proteins, Transcription factors, Transporters
- Subcellular location
- Nuclear bodies,Aggresome
OverviewNCBI Gene
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]
Canonical amino-acid sequenceUniProt
337 residues, UniProt reviewed canonical sequence.
>Q9UBP5|HEY2
1 MKRPCEETTS ESDMDETIDV GSENNYSGQS TSSVIRLNSP TTTSQIMARK KRRGIIEKRR
61 RDRINNSLSE LRRLVPTAFE KQGSAKLEKA EILQMTVDHL KMLQATGGKG YFDAHALAMD
121 FMSIGFRECL TEVARYLSSV EGLDSSDPLR VRLVSHLSTC ATQREAAAMT SSMAHHHHPL
181 HPHHWAAAFH HLPAALLQPN GLHASESTPC RLSTTSEVPP AHGSALLTAT FAHADSALRM
241 PSTGSVAPCV PPLSTSLLSL SATVHAAAAA ATAAAHSFPL SFAGAFPMLP PNAAAAVAAA
301 TAISPPLSVS ATSSPQQTSS GTNNKPYRPW GTEVGAFLocalizationUniProt · AlphaFold · HPA
Whether an antibody against HEY2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.6
- Highest tissue expression
- 71 nTPM
Expression across tissuesHPA
Tissue
- blood vessel: 71 nTPM
- heart muscle: 29 nTPM
- skeletal muscle: 16 nTPM
- epididymis: 16 nTPM
- fallopian tube: 13 nTPM
- basal ganglia: 9.5 nTPM
Single-cell type
- granulosa cells: 165 nCPM
- cardiomyocytes: 156 nCPM
- vascular smooth muscle cells: 111 nCPM
- late spermatids: 105 nCPM
- oocytes: 101 nCPM
- epididymal principal cells: 77 nCPM
Immune cell
- gdT-cell: 0.5 nTPM
- naive CD8 T-cell: 0.2 nTPM
- memory CD8 T-cell: 0.1 nTPM
- naive CD4 T-cell: 0.1 nTPM
- basophil: 0 nTPM
- classical monocyte: 0 nTPM
Brain region
- spinal cord: 27 nTPM
- medulla oblongata: 23 nTPM
- white matter: 22 nTPM
- basal ganglia: 22 nTPM
- hypothalamus: 21 nTPM
- midbrain: 18 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about HEY2.
Disease | GeneticClinVar
1 pathogenic / likely-pathogenic of 67 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.41
- gnomAD pLI
- 0.89
- gnomAD missense Z
- 0.85
- DepMap mean gene effect
- 0.22
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- anterior/posterior axis specification
- anterior/posterior pattern specification
- aortic valve morphogenesis
- arterial endothelial cell differentiation
- ascending aorta morphogenesis
- atrial septum morphogenesis
- cardiac conduction system development
- cardiac epithelial to mesenchymal transition
- cardiac left ventricle morphogenesis
- cardiac muscle cell apoptotic process
- cardiac muscle cell proliferation
- cardiac muscle hypertrophy in response to stress
- cardiac right ventricle morphogenesis
- cardiac septum morphogenesis
- cardiac vascular smooth muscle cell development
- cardiac ventricle morphogenesis
- cell fate commitment
- circulatory system development
- cochlea development
- coronary vasculature morphogenesis
- dorsal aorta morphogenesis
- endocardial cushion to mesenchymal transition involved in heart valve formation
- epithelial to mesenchymal transition involved in endocardial cushion formation
- heart trabecula formation
- labyrinthine layer blood vessel development
- mesenchymal cell development
- muscular septum morphogenesis
- negative regulation of biomineral tissue development
- negative regulation of cardiac muscle cell apoptotic process
- negative regulation of DNA-templated transcription
- negative regulation of gene expression
- negative regulation of Notch signaling pathway
- negative regulation of smooth muscle cell differentiation
- negative regulation of transcription by RNA polymerase II
- negative regulation of transcription initiation by RNA polymerase II
- Notch signaling pathway
- outflow tract morphogenesis
- positive regulation of cardiac muscle cell proliferation
- positive regulation of heart rate
- positive regulation of transcription by RNA polymerase II
- protein-DNA complex assembly
- pulmonary artery morphogenesis
- pulmonary valve morphogenesis
- regulation of inner ear auditory receptor cell differentiation
- regulation of neurogenesis
- regulation of transcription by RNA polymerase II
- regulation of vasculogenesis
- smooth muscle cell differentiation
- tricuspid valve formation
- tricuspid valve morphogenesis
- umbilical cord morphogenesis
- vascular associated smooth muscle cell development
- vasculogenesis
- ventricular cardiac muscle cell development
- ventricular septum morphogenesis
- ventricular trabecula myocardium morphogenesis
- negative regulation of cardiac vascular smooth muscle cell differentiation
Molecular functions
- cis-regulatory region sequence-specific DNA binding
- DNA-binding transcription factor activity
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription repressor activity, RNA polymerase II-specific
- histone deacetylase binding
- identical protein binding
- protein dimerization activity
- RNA polymerase II cis-regulatory region sequence-specific DNA binding
- RNA polymerase II-specific DNA-binding transcription factor binding
- sequence-specific DNA binding
- sequence-specific double-stranded DNA binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of HEY2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads HEY2 as an antibody target. Whether an autoantibody or antibody against HEY2 could matter depends on whether native HEY2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
HEY2 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label HEY2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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