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FLASH GENE
Symbol CCAR2 contributors: mct - updated : 04-07-2015
HGNC name KIAA1967
HGNC id 23360
Location 8p22      Physical location : -
Genatlas name
  • deleted in breast cancer
  • Synonym name
  • p30 DBC protein
  • Synonym symbol(s) DBC-1, DBC1, p30 DBC, DBC2, NET35, p30 DBC, KIAA1967
    DNA
    TYPE functioning gene
    STRUCTURE 15.84 kb     20 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    text variants 1 and 2 encode the same protein
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    20 - 4012 103 923 - 2008 18235501
    - - 3749 103 923 - 2008 18235501
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    HOMOLOGY
    Homologene
    FAMILY
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,matrix
    intracellular,nucleus
    basic FUNCTION
  • promoting TP53-mediated apoptosis through specific inhibition of SIRT1
  • may be an important regulator of heterochromatin formation and genomic stability by disrupting the SUV39H1-SIRT1 complex and inactivating both enzymes
  • involved in cell proliferation, apoptosis and histone modification, all processes important for regulating tumorigenesis
  • role in regulating ESR2-dependent gene expressions
  • its expression inhibits the transactivation of the SIRT1 promoter mediated by full-length BRCA1
  • may modulate the cellular functions of BRCA1 and have important implications in the understanding of carcinogenesis in breast tissue
  • regulator of some nuclear receptors, the methyltransferase SUV39H1, and the NAD-dependent deacetylase SIRT1
  • endogenous inhibitor of HDAC3
  • new regulator of HDAC3 and is a negative regulator of two key distinct deacetylases, SIRT1 and HDAC3
  • KIAA1967 and SIRT1 play reciprocal roles as major regulators of ESR1 activity, by regulating DNA binding by ESR1 and by regulating co-activator synergy
  • is a large, predominantly nuclear, multidomain protein that modulates gene expression by inhibiting several epigenetic modifiers, including the deacetylases SIRT1 and HDAC3, and the methyltransferase SUV39H1
  • CCAR2 and CCAR1 are largely disordered proteins that have evolved from one common ancestor
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • KIAA1967 and ZNF326 (which we call ZNF-protein interacting with nuclear mRNPs and KIAA1967 (ZIRD)) as subunits of a novel protein complex--named DBIRD--that binds directly to RNAPII
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with SIRT1
  • binds to the SUV39H1 catalytic domain and inhibits its ability to methylate histone H3
  • interaction with ESR2 (negatively regulates the ligand-dependent transcriptional activation function of ESR2, and RNA interference-mediated depletion of DBC1 stimulates the transactivation function of ESR2)
  • physical interaction between the N-terminus of KIAA1967 and the C-terminus of BRCA1, also known as the BRCT domain
  • function as a negative regulator of the NAD-dependent protein deacetylase SIRT1
  • CCAR1 binding protein (associates directly with ESR1 and cooperates synergistically with CCAR1 to enhance ESR1 function)
  • CCAR2 phosphorylation by ATM/ATR inhibits SIRT1 deacetylase in response to DNA damage
  • CCAR2 is a novel regulator of NR1D1 and modulates the NR1D1 repressor function
  • KAT8 binding and acetylation of CCAR2 are inhibited after DNA damage in an ATM-dependent fashion, contributing to increased SIRT1-CCAR2 binding after DNA damage
  • inactivation of CHEK2 reduces CCAR2-SIRT1 binding, thus preventing TP53 acetylation and CCAR2-induced apoptosis
  • reduced UCP1 expression under inflammation is mediated by the increased expression of DBC1, which inhibits SIRT1 activity
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in esophageal squamous cell carcinoma correlates with poor prognosis
    tumoral     --other  
    with overexpression of SIRT1 is associated with poor prognosis of gastric carcinoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • could be a prognostic biomarker in esophageal squamous cell carcinoma
  • Therapy target
    ANIMAL & CELL MODELS