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FLASH GENE
Symbol HIC1 contributors: mct - updated : 24-05-2014
HGNC name hypermethylated in cancer 1
HGNC id 4909
Location 17p13.3      Physical location : 1.958.392 - 1.962.980
Synonym name see TSG17D
Synonym symbol(s) ZBTB29, ZNF901, hic-1
DNA
TYPE functioning gene
STRUCTURE 4.59 kb     2 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter (TATA box)
cytosine-phosphate-guanine/HTF
text structure
  • a p53 binding site in the 5' flanking region
  • two alternative 5' exons, 1a and 1b fused to a large second coding exon 2, and a long 5'-UTR sequence, called 1c which encompass the G-C-rich promoter associated with exon 1a and uses the same splice donor site
  • exon 1a is a noncoding exon associated with a major G-C-rich promoter whereas exon 1b is a downstream coding exon associated with a minor TATA box promoter
    • MAPPING cloned Y linked N status confirmed
    Map pter - D17S643 ,D17S695 - D17S28 - HIC1 ,D17S5 ,SMG6 ,D17S654 ,D17S379 - D17S128 - D17S675 - PFN1 - cen
    Authors Wilgenbus (96), Hoff (00)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 3174 - 714 - 2009 1901563
  • isoform 1
    • 2 - 3071 - 733 - 2009 1901563
  • isoform 2
    		•
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticthymus   highly
    Digestiveintestinelarge intestinecolon highly
    Reproductivefemale systemovary  highly
     male systemprostate  highly
    Respiratorylung   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, fetal
    Text mesenchymes apposed to the precartilaginous condensations,muscles,sclerosomes,body wall,limb
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • five C2H2 type zinc finger domains
  • a poxvirus and a zinc finger BTB-POZ domain
    • conjugated Acetylated , sumoylated
    HOMOLOGY
    interspecies homolog to murine Hic1 (95.3pc)
    homolog to rattus Hic1 (93.8pc)
    intraspecies homolog to HIC2
    Homologene
    FAMILY
  • C2H2-type zinc finger protein family
  • HIC transcription factor subfamily
    • CATEGORY regulatory , transcription factor , tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • transcriptional repressor, may be involved in development of head, face, limbs and ventral body wall
  • tumor suppressor in a subset of diffuse large B-cell lymphomas (DLBCLs)
  • involved in p53- and E2F1-dependent cell survival and stress responses (Van Rechem 2009)
  • regulating ATOH1, FGFBP1, SIRT1, E2F1, CXCR7 (Van Rechem 2009)
  • involved in growth control since it recruits SMARCA4 to repress transcription of E2F1 (Van Rechem 2009)
  • attenuates Wnt signalling by recruiting TCF4 and beta catenin to the nuclear bodies (Valenta 2006)
  • spatially restricts EPHA1 expression in development, and upregulated expression of EPHA1 resulting from epigenetic silencing of HIC1 in cancer cells may be an important mechanism in epithelial malignancy
  • transcriptional repressor involved in the regulation of growth control and DNA damage response
  • regulates DNA repair in a SUMO-dependent way
  • transcriptional repressor involved in cell migration properties
    • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS development
    text transcriptional repressor
    PATHWAY
    metabolism
    signaling
    a component
  • HIC1 forms complexes with the signal transducers and activators of transcription 3 (STAT3) and attenuates STAT3-mediated transcription
    • INTERACTION
    DNA binding to the SIRT1 promoter
    RNA
    small molecule
    protein
  • CTBP
  • forming a transcriptional repression complex with SIRT1 deacetylase
  • interacting with ARID1A (Van Rechem 2009)
  • repressing ATOH1 (Briggs 2008)
  • direct transcriptional repressor of the gene encoding EPHA1, a cell surface ligand implicated in the pathogenesis of epithelial cancers
  • EPHA2 is a new direct target gene of HIC1
  • is a direct transcriptional repressor of CDKN1A and HIC1 is a key player in the regulation of the DNA damage response
  • role of HIC1 in antagonizing STAT3-mediated activation of VEGFA and MYC gene expression and cell growth
  • CXCR7, ADRB2 and the tyrosine kinase receptor EPHA2 are direct target genes of HIC1
  • HIC1 is a direct transcriptional repressor of LRP8 and VLDLR
    • cell & other
    REGULATION
    Other regulated by an acetylation/deacetylation-SUMOylation switch (Stankovic-Valentin 2007)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   deletion    
    in Miller-Dieker syndrome
    tumoral     --low  
    in medulloblastoma by altered CpG island methylation
    tumoral   LOH   loss of function
    by hypermethylation, in breast ductal carcinomas
    tumoral     --low  
    by hypermethylation and hypermethylation of its promoter results in loss of its repressive function, responsible for prostate cancer progression and invasion
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • HIC1-LCN2 axis may serve as a subtype-specific prognostic biomarker in triple-negative breast cancer
    • Therapy target
    ANIMAL & CELL MODELS
    putatively involved in the pathogenesis as suggested by the developmental defects observed in Hic1 deficient mice