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Symbol HEY1 contributors: mct - updated : 23-10-2015
HGNC name hairy/enhancer-of-split related with YRPW motif 1
HGNC id 4880
Location 8q21.13      Physical location : 80.676.245 - 80.680.098
Synonym name
  • HES-related repressor protein 2
  • cardiovascular helix-loop-helix factor 2
  • hairy-related transcription factor 1
  • class B basic helix-loop-helix protein 31
  • Synonym symbol(s) HESR-1, CHF2, HESR1, HRT-1, CHF-2, HERP2, BHLHb31, OAF1, MGC1274
    TYPE functioning gene
    STRUCTURE 3.86 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    motif repetitive sequence   ALU   long interspersed repetitive elements
    MAPPING cloned   linked   status provisional
    Physical map
    MRPL9P1 8q21.11 mitochondrial ribosomal protein L9 pseudogene ZFH4 8q13.3 mitochondrial ribosomal protein L9 pseudogene PXMP3 8q21.1 peroxisomal membrane protein 3, 35kDa (Zellweger syndrome) PKIA 8q13-q21.3 protein kinase (cAMP-dependent, catalytic) inhibitor alpha CGI-62 8q21.11 CGI-62 protein IL7 8q12-q13 interleukin 7 STMN2 8p13.2 stathmin-like 2 HEY1 8q21 hairy/enhancer-of-split related with YRPW motif 1 MRPS28 8q21.1-q21.2 mitochondrial ribosomal protein S28 TPD52 8q21 tumor protein D52 LOC389671 8 LOC389671 LOC392236 8 similar to ribosomal protein L13a; 60S ribosomal protein L13a; 23 kD highly basic protein LOC340443 8q21.12 similar to ribosomal protein S5; 40S ribosomal protein S5 RINZF LOC389672 8 similar to 40S ribosomal protein SA (P40) (34/67 kDa laminin receptor) (Colon carcinoma laminin-binding protein) (NEM/1CHD4) (Multidrug resistance-associated protein MGr1-Ag) LOC392237 8 similar to mitochondrial carrier triple repeat 1 CKS1A 8q21 CDC28 protein kinase regulatory subunit 1A PAG 8q21.13 CDC28 protein kinase regulatory subunit 1A LOC392238 8 LOC392238 LOC392239 FABP5 15q12-q24.3 fatty acid binding protein 5 (psoriasis-associated) PMP2 8q21.3-q22.1 peripheral myelin protein 2 FABP4 8q21 fatty acid binding protein 4, adipocyte LOC389673 8 similar to Myelin P2 protein LOC392240 8 similar to hypothetical protein MGC5466 IMPA1 8q21.2-q21.3 inositol(myo)-1(or 4)-monophosphatase 1 FLJ14007 8q21.13 hypothetical protein FLJ14007 Shax3 8q21.13 Snf7 homologue associated with Alix 3 SNX16 8q21.13 sorting nexin 16 LOC389674 8 similar to Heterogeneous nuclear ribonucleoprotein A1 (Helix-destabilizing protein) (Single-strand binding protein) (hnRNP core protein A1) (HDP-1) (Topoisomerase-inhibitor suppressed)
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 2319 32.6 304 - 2000 10860664
    5 - 2331 33.1 308 - 2000 10860664
    also called HESR1-12nt or variant 2/isoform b
    2 - 2052 - 214 - 2000 10860664
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Hearing/Equilibriumearinnercochlea highly
    Nervousnerve   highly
    Respiratoryrespiratory tracttrachea  highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier/liningnasal epithelium  
    Muscularstriatum  highly Homo sapiens
    cell lineage
    cell lines
    at STAGE
    physiological period embryo, fetal
    Text tissues, somitic mesoderm, in the developing cochlea
  • basic helix-loop-helix (HLH) N terminal domain
  • an orange domain
  • a YRPW motif
  • a protein protein interaction motif near the C terminus
    interspecies homolog to murine Hey1
  • basic helix-loop-helix family of trasncription factor HERP
  • Hairy/Enhancer-of-split-related with YRPW-like motif (HEY) family of proteins
  • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    basic FUNCTION
  • implicated in cell fate decision and boundary formation
  • involved in dopamine-related polygenic disorders and behavioral traits
  • invoved in controlling Notch induced endocardial epithelial to mesenchymal transition, a process critical for valve and septum formation
  • with HEY2, are the downstream mediators of the prosensory function of Notch in early cochlear development
  • AR-selective corepressor that contains both HDAC-dependent and -independent repression domains
  • through its interplay with RUNX2, may play an important role in regulating BMP9-induced osteoblast lineage differentiation of pluripotent mesenchymal stem cells
  • inhibits myogenesis by associating with and repressing expression of key myogenic targets
  • HESR family (HEY1, HEY2, HEYL)is involved in dopamine transporter (SLC6A3) expression via the VNTR domain
  • HEY1 and HEY2 selectively repress androgen receptor (AR) signaling in mammalian cell lines
  • HEY1 and HEYL (which are known Notch target genes) are expressed simultaneously in skeletal muscle only in satellite cells
  • HEY1 and HEYL are essential for the generation of adult satellite cells and for the maintenance of skeletal muscle homeostasis
  • critical scaffolding function for HEY1, HEY2 that is required for forming an active retrotranslocation complex containing SYVN1, SEL1L, and DERL2
  • information provided by HES1/HEY1 downstream of NOTCH1 as well as myogenic regulatory factors (MRFs) activities are integrated at the level of the CDKN1C enhancer to regulate the decision between progenitor cell maintenance and muscle differentiation
  • 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
  • HEY1 augmented the metastasis of osteosarcoma via upregulation of MMP9 expression
  • CELLULAR PROCESS nucleotide, transcription
    cell organization/biogenesis
    a component
    small molecule
  • with NOTCH1 (primary target gene of NOTCH1)
  • interacts with HEYL
  • may be a direct target of the GDF2-induced Smad signaling pathway
  • through its interplay with RUNX2, may play an important role in regulating GDF2-induced osteoblast lineage differentiation of mesenchymal stem cells
  • interaction with RUNX2 (RUNX2 act synergistically in BMP9-induced osteogenic differentiation, and RUNX2 expression significantly decreased in the absence of HEY1 suggesting that RUNX2 may function downstream of HEY1
  • recruited to the promoter regions of myogenin and MEF2C, two genes whose induction is critical for myogenesis
  • ADAM10-dependent regulation of DLL1 and DLL4 expression in association with changes in HES1 and HEY1 expression
  • MMP9 was a downstream effector of HEY1 that promotes the invasion of osteosarcoma cells
  • HEY1 mediated nuclear translocation of FBXO45 and its associated ubiquitin ligase complex may extend its spectrum to additional nuclear targets triggering their ubiquitination
  • cell & other
    activated by NOTCH1
    MSX1 (strongly up-regulated the Delta-Notch pathway genes DLK1, NOTCH3, and HEY1)
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    inactivation of HEY1 and HEYL, two primary target genes of Notch, causes severe heart malformations, including membranous ventricular septal defects and dysplastic atrioventricular and pulmonary valves
    tumoral     --over  
    in glioblastoma)
    tumoral       gain of function
    in human osteosarcoma
    tumoral fusion      
    HEY1-NCOA2 fusion in mesenchymal chondrosarcoma
    Variant & Polymorphism
    Candidate gene
    Marker molecular marker to distinguish glioblastoma multiforme patients with a longer survival prognosis from those at high risk
    Therapy target
    inhibition of HEY1 may be a novel therapeutic strategy for preventing osteosarcoma metastasis
    therapeutic target for glioblastoma patients