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FLASH GENE
Symbol DKC1 contributors: mct/ - updated : 05-11-2014
HGNC name dyskeratosis congenita 1, dyskerin
HGNC id 2890
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveesophagus   highly
Endocrinethyroid   highly
Reproductivefemale systemuteruscervix highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectiveadipose  highly
cell lineage hemopoietic system
cell lines
fluid/secretion
at STAGE
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
  • 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