Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol DKC1 contributors: mct/ - updated : 05-11-2016
HGNC name dyskeratosis congenita 1, dyskerin
HGNC id 2890
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • multiple nuclear localization signals (NLS)
  • two TruB pseudouridine synthase motifs (PUA/THUMP)
  • multiple phosphorylation sites
  • N and C terminal lysine-rich repeat domains
    • HOMOLOGY
    interspecies ortholog to rattus Nap57
    ortholog to yeast S.cerevisiae Cbf5p
    Homologene
    FAMILY
  • pseudouridine synthase TRUB family
    • CATEGORY enzyme , RNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm,nuclear bodies,coiled bodies (Cajal)
    intracellular,nucleus,nucleolus
    text
  • located in the nucleus (nucleolar and the coiled bodies) and nucleolus
  • pre-rRNA processing factors such as DKC1 and fibrillarin (FBL) associate with r-chromatin during interphase, but were released from r-chromatin in mitosis
  • redistributed from the nucleolus in interphase cells to the perichromosomal region during prometaphase, metaphase and anaphase
    • basic FUNCTION
  • catalytic subunit of the H/ACA box small nucleolar RNA particles responsible for the site specific pseudouridination of rRNA
  • required for ribosome biogenesis and telomere maintenance
  • important for the biogenesis of ribosomes, spliceosomal small nuclear ribonucleoproteins (RNPs), microRNAs and the telomerase RNP
  • participates in at least two distinct nuclear functional complexes: the H/ACA small nucleolar ribonucleoproteic complex involved in RNA pseudouridylation and the active telomerase complex
  • DKC1 nucleolar and cytoplasmic functions might cumulatively account for the plethora of manifestations displayed by DKC1 syndrome 7)
  • also implicated in telomere maintenance
  • promotes TERT stability, endorsing the development of TERT supplementation strategies for the treatment of DKC1
  • its depletion increases VEGF mRNA internal ribosome entry site-mediated translation
  • involved in multiple functions related to cell growth, proliferation, and telomere maintenance
  • is a highly dynamic protein throughout the cell cycle and increases the repertoire of fundamental cellular processes that are disrupted by absence of its normal function
  • required for both ribosome biogenesis and telomerase complex stabilization
  • embryonic stem cells (ESCs), ubiquitously express NOP10 and DKC1, stabilizing components of telomerase complexes
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    text rRNA synthesis
    PATHWAY
    metabolism
    signaling
    a component
  • telomerase complex associating with GAR1, NHP2, NOLA3, TERC
  • DKC1-NOP10-NHP2 core trimer specifically recognizes H/ACA RNAs
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • may be a direct transcriptional target of MYC
  • interaction with SHQ1 (H/ACA RNP assembly factor SHQ1 is the protein specifically binding to the DKC1 domains forming the DKC1 mutation cluster)
  • interaction with TERC (assembles not one but two sets of all four of the H/ACA RNP core proteins, dyskerin, NOP10, NHP2, and GAR1)
  • pontin and reptin (RUVBL1 and RUVBL2) (as components of the R2TP complex) are required to pry DKC1 from SHQ1
  • SMUG1 is a DKC1 interaction partner that contributes to rRNA quality control, partly by regulating 5-hydroxymethyluridine levels
  • rRNA gene chromatin (r-chromatin) association of NOLC1, DKC1, and FBL was dependent on the transcription factor upstream binding factor (UBF)
    • cell & other
  • centromere/microtubule binding
    • REGULATION
    Other dyskerin stability is regulated by SUMOylation and mutations altering dyskerin SUMOylation can lead to defects in telomere maintenance
    ASSOCIATED DISORDERS
    corresponding disease(s) DKC1 , HHS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in neoplasia
    constitutional       loss of function
    impairments in DKC1 function also lead to defects in TP53 internal ribosome entry site-dependent activity in DKC1 patient cells
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    inhibition of human dyskerin is a new approach to target ribosome biogenesis in cancer
    ANIMAL & CELL MODELS