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FLASH GENE
Symbol DKC1 contributors: mct/ - updated : 05-11-2014
HGNC name dyskeratosis congenita 1, dyskerin
HGNC id 2890
Corresponding disease
DKC1 dyskeratosis congenita
HHS Hoyeraal-Hreidarsson syndrome
Location Xq28      Physical location : 153.991.030 - 154.005.963
Synonym name
  • nucleolar protein family A, member 4 (H/ACAA) small nucleolar protein
  • H/ACA ribonucleoprotein complex subunit 4
  • snoRNP protein DKC1
  • Synonym symbol(s) DKC, NAP57, NOLA4, XAP101, dyskerin
    DNA
    TYPE functioning gene
    SPECIAL FEATURE opposite orientation, tail to tail
    text
  • tail to tail with MMP1 (palmitoylated erythrocyte membrane protein) gene
  • STRUCTURE 14.93 kb     15 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    motif repetitive sequence   triplet
    MAPPING cloned Y linked Y status confirmed
    Physical map
    TAZ Xq28 tafazzin (cardiomyopathy, dilated 3A (X-linked); endocardial fibroelastosis 2; Barth syndrome) ATP6AP1 Xq28 ATPase, H+ transporting, lysosomal accessory protein 1 GDI1 Xq28 GDP dissociation inhibitor 1 DXS9928E Xq28 DNA segment on chromosome X (unique) 9928 expressed sequence PLXN3 Xq28 likely ortholog of mouse plexin 3 DXS9879E Xq28 DNA segment on chromosome X (unique) 9879 expressed sequence UBL4 Xq28 ubiquitin-like 4 SLC10A3 Xq28 solute carrier family 10 (sodium/bile acid cotransporter family), member 3 FAM3A Xq28 family with sequence similarity 3, member A G6PD Xq28 glucose-6-phosphate dehydrogenase IKBKG Xq28 inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma SPCX Xq28 SPCX LAGE2A  cancer/testis antigen 1-A CTAG1 Xq28 cancer/testis antigen 1 LOC340600 Xq28 cyclic-AMP-dependent transcription factor ATF-4 pseudogene deltaNEMO Xq28 deltaNEMO CTAG2 Xq28 cancer/testis antigen 2 LOC392561 X similar to olfactory receptor MOR255-2 GAB3 Xq28 GRB2-associated binding protein 3 DKC1 Xq28 dyskeratosis congenita 1, dyskerin MPP1 Xq28 membrane protein, palmitoylated 1, 55kDa LOC158957 Xq28 hypothetical LOC158957 F8 Xq28 coagulation factor VIII, procoagulant component (hemophilia A) HCBP6 Xq28 hepatitis C virus core-binding protein 6
    regionally located 60kb centromeric to F8
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    15 - 2579 58 509 - 2013 24219293
    15 - 2594 57.7 514 - 2013 24219293
    14 splicing 3097 47.6 420 - 2011 21820037
  • unexpected cytoplasmic localization
  • truncated form of dyskerin
  • can play a further, unpredicted role in cell adhesion
  • 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