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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
    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
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 2672 - 337 - - 10860664
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheartventricle    Homo sapiensFetal
    Nervousbrainforebraincerebral cortex  
    Respiratoryrespiratory tractlarynx  highly
    Visualeyeretina  highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    cell lineage
    cell lines
    at STAGE
    physiological period embryo, fetal
    Text lateral plate mesoderm before vessel formation, in the developing cochlea
  • 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
    interspecies homolog to zebrafish gridlock
    homolog to murine Hey2 (94,07 pc)
    homolog to rattus Hey2 (94,66 pc)
  • 'hairy/enhancer of split' family of bHLH proteins
  • HEY family
  • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    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
    a component
  • binding
  • RNA
    small molecule
  • 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
    activated by NOTCH1
    induced by highly induced by ER stress
    corresponding disease(s)
  • 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
    Therapy target