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FLASH GENE
Symbol HEY2 contributors: mct - updated : 11-01-2013
HGNC name hairy/enhancer-of-split related with YRPW motif 2
HGNC id 4881
Location 6q22.31      Physical location : 126.070.731 - 126.082.414
Synonym name
  • gridlock
  • HES-related protein 1, gridlock
  • class B basic helix-loop-helix protein 32
  • hairy-related transcription factor 2
  • cardiovascular helix-loop-helix factor 1
  • HES-related repressor protein 2
  • Synonym symbol(s) GRL, HERP1, HRT2, CHF1, GRIDLOCK, HESR2, bHLHb32, MGC10720, HERP
    DNA
    TYPE functioning gene
    STRUCTURE 11.68 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    motif repetitive sequence   ALU   long interspersed repetitive elements
    MAPPING cloned Y linked N status confirmed
    Physical map
    C6orf170 6q22.32 chromosome 6 open reading frame 170 GJA1 6q22.3 gap junction protein, alpha 1, 43kDa (connexin 43) LOC260339 6q22.32 processed pseudogene mtTFA 3 LOC391966 6 similar to ADP,ATP carrier protein, fibroblast isoform (ADP/ATP translocase 2) (Adenine nucleotide translocator 2) (ANT 2) LOC391967 6 similar to 60S ribosomal protein L23a HSF2 6q22.33 heat shock transcription factor 2 TDE2 6q22.32 tumor differentially expressed 2 PKIB 6q22.32 protein kinase (cAMP-dependent, catalytic) inhibitor beta FABP7 6q22-q23 fatty acid binding protein 7, brain SMPDL3A 6q22.32 sphingomyelin phosphodiesterase, acid-like 3A C6orf213 6q22.32 chromosome 6 open reading frame 213 TRDN 6q22-q23 triadin TCBA1 6q21-q22 T-cell lymphoma breakpoint associated target 1 IBRDC1 6q22.33 IBR domain containing 1 TPD52L1 6q22-q23 tumor protein D52-like 1 C6orf74 6q13-q24.3 chromosome 6 open reading frame 74 LOC256096 6q22.33 hypothetical LOC256096 HEY2 6q22.2-q22.33 hairy/enhancer-of-split related with YRPW motif 2 NCOA7 6q22.33 nuclear receptor coactivator 7 HINT3 6q22.33 histidine triad nucleotide binding protein 3 C6orf75 6q11.1-q22.33 chromosome 6 open reading frame 75 LOC391968 6 similar to PPP1R14B protein LOC389426 6 LOC389426 LOC391969 6 similar to ribosomal protein S4, X-linked LOC389427 6 similar to MGC32805 protein THSD2 6q22.33 thrombospondin, type I, domain 2 RNF146 6q22.1-q22.33 ring finger protein 146 ECHDC1 6q22.33 enoyl Coenzyme A hydratase domain containing 1 LOC246737 6q23.1 tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta pseudogene LOC389428 6 similar to ribosomal protein L5; 60S ribosomal protein L5 KIAA0408 6q22.33 KIAA0408 LOC389429 6 similar to RIKEN cDNA 2310057J18 MRPS17P5 6q22.33 mitochondrial ribosomal protein S17 pseudogene 5 PTPRK 6q22.2-q22.3 protein tyrosine phosphatase, receptor type, K LOC391970 6 similar to eukaryotic translation elongation factor 1 delta (guanine nucleotide exchange protein) LAMA2 6q22-q23 laminin, alpha 2 (merosin, congenital muscular dystrophy) LOC338470 6q22-q23 mesoderm specific transcript homolog (mouse) pseudogene ARHGAP18 6q23.1 Rho GTPase activating protein 18 C6orf191 6q23.1 chromosome 6 open reading frame 191 L3MBTL3 6q23 l(3)mbt-like 3 (Drosophila) SAMD3 6q23.1 sterile alpha motif domain containing 3 KIAA1913 6q23.1 KIAA1913
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 2672 - 337 - - 10860664
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheartventricle    Homo sapiensFetal
    Hearing/Equilibriumearinnercochlea  
    Nervousbrainforebraincerebral cortex  
    Respiratoryrespiratory tractlarynx  highly
    Visualeyeretina  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Connectivebone   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, fetal
    Text lateral plate mesoderm before vessel formation, in the developing cochlea
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • orange domain
  • UBL domain of HEY2 that seems to have a function independent of DERL2 recruitment in ERAD
  • N-terminal bHLH domain
  • a protein-protein interaction motif near the C terminus
  • HOMOLOGY
    interspecies homolog to zebrafish gridlock
    homolog to murine Hey2 (94,07 pc)
    homolog to rattus Hey2 (94,66 pc)
    Homologene
    FAMILY
  • 'hairy/enhancer of split' family of bHLH proteins
  • HEY family
  • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleolus
    basic FUNCTION
  • involved in regulation of transcription, DNA-dependent, histogenesis and organogenesis, neurogenesis
  • may function as a transcriptional repressor
  • may be involved in the regulation of ventricular septation in humans
  • suppresses atrial identity in the left ventricular compact myocardium, facilitates myocardial proliferation by suppressing TBX5, and thereby promotes proper ventricular myocardial maturation
  • with HEY1, are the downstream mediators of the prosensory function of Notch in early cochlear development
  • functions in parallel with HES1 and HES5 in patterning the organ of Corti, and interacts genetically with HES1 for early embryonic development and survival
  • its expression levels influence hypertrophy and the progression to heart failure in response to pressure overload through modulation of apoptosis and GATA4 activity
  • potentially regulating the later steps of coronary vascular development in both a myocardial-dependent, non-cell autonomous fashion and likely a vascular cell-specific effect as well
  • HESR family (HEY1, HEY2, HEYL)is involved in dopamine transporter expression (SLC6A3) via the VNTR domain
  • HEY1 and HEY2 selectively repress androgen receptor (AR) signaling in mammalian cell lines
  • play an important role in regulation of vascular smooth muscle phenotype and gene expression
  • involved in the transcriptional regulation of MMP10
  • transcriptional regulator of cardiac electrical function involved in the pathogenesis of Brugada syndrome
  • critical scaffolding function for HEY1, HEY2 that is required for forming an active retrotranslocation complex containing SYVN1, SEL1L, and DERL2
  • critical role for HEY1 and HEY2 in prosensory cell maintenance and identifies Hedgehog signaling as a novel upstream regulator of their prosensory function in the mammalian cochlea
  • important role of HEY1 and HEY2 in endothelial cells during early vascular development
  • CELLULAR PROCESS cell life
    nucleotide, transcription, regulation
    cell organization/biogenesis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
  • binding
  • RNA
    small molecule
    protein
  • heterodimerization with HELT by the bHLH domain
  • interacting with TBX5
  • interacts genetically with HES1 for early embryonic development and survival is an important
  • regulator of MMP10 expression (HEY2 represses MMP10 expression)
  • cell & other
    REGULATION
    activated by NOTCH1
    induced by highly induced by ER stress
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
  • to atrioventricular septal defects (minor role)
  • to hypertrophy and heart failure
  • to Brugada syndrome
  • Variant & Polymorphism other
  • genetic polymorphisms in HEY2 may affect susceptibility to hypertrophy and heart failure
  • rs9388451 associate to Brugada syndrome
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS