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FLASH GENE

Symbol

DKC1

contributors: mct/ - updated : 05-11-2016

HGNC name	dyskeratosis congenita 1, dyskerin
HGNC id	2890

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

regionally located

60kb centromeric to F8

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001142463 15 - 2579 NP_001135935 58 509 - 2013 24219293 NM_001363 15 - 2594 NP_001354 57.7 514 - 2013 24219293 NM_001288747 14 splicing 3097 NP_001275676 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)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive esophagus       highly Endocrine thyroid       highly Reproductive female system uterus cervix   highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose     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
	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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed cancer     inhibition of human dyskerin is a new approach to target ribosome biogenesis in cancer

ANIMAL & CELL MODELS