Dyskerin

"DKC1" redirects here. For the 1994 video game, see Donkey Kong Country.

H/ACA ribonucleoprotein complex subunit 4 is a protein that in humans is encoded by the DKC1 gene.^[5][6][7] The encoded protein, known as dyskerin, is a highly conserved nucleolar enzyme that plays key roles in rRNA modification, telomerase function, and ribosome biogenesis.

DKC1
Identifiers
Aliases	DKC1, CBF5, DKC, DKCX, NAP57, NOLA4, XAP101, Dyskerin, dyskerin pseudouridine synthase 1
External IDs	OMIM: 300126; MGI: 1861727; HomoloGene: 1045; GeneCards: DKC1; OMA:DKC1 - orthologs
Gene location (Human) Chr. X chromosome (human)[1] Band Xq28 Start 154,762,742 bp[1] End 154,777,689 bp[1]
Gene location (Mouse) Chr. X chromosome (mouse)[2] Band X|X A7.3 Start 74,139,460 bp[2] End 74,153,383 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in secondary oocyte sural nerve gingival epithelium hair follicle tibia tendon of biceps brachii pancreatic ductal cell Achilles tendon epithelium of nasopharynx cartilage tissue Top expressed in hand tail of embryo primitive streak otic vesicle epiblast zygote genital tubercle secondary oocyte embryo abdominal wall More reference expression data BioGPS More reference expression data
Gene ontology Molecular function telomerase activity pseudouridine synthase activity isomerase activity box H/ACA snoRNA binding protein binding telomerase RNA binding RNA binding Cellular component cytoplasm Cajal body box H/ACA telomerase RNP complex box H/ACA scaRNP complex telomerase holoenzyme complex box H/ACA snoRNP complex nucleus fibrillar center nucleoplasm nucleolus Biological process pseudouridine synthesis RNA processing ribosome biogenesis positive regulation of establishment of protein localization to telomere telomerase RNA stabilization box H/ACA RNA metabolic process positive regulation of telomere maintenance via telomerase snRNA pseudouridine synthesis positive regulation of telomerase activity positive regulation of telomerase RNA localization to Cajal body rRNA processing RNA modification cell population proliferation mRNA pseudouridine synthesis box H/ACA RNA 3'-end processing rRNA pseudouridine synthesis telomere maintenance via telomerase regulation of telomerase RNA localization to Cajal body Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1736 245474 Ensembl ENSG00000130826 ENSMUSG00000031403 UniProt O60832 Q9ESX5 RefSeq (mRNA) NM_001142463 NM_001288747 NM_001363 NM_001030307 NM_001359411 NM_001359412 NM_001359413 RefSeq (protein) NP_001135935 NP_001275676 NP_001354 NP_001025478 NP_001346340 NP_001346341 NP_001346342 Location (UCSC) Chr X: 154.76 – 154.78 Mb Chr X: 74.14 – 74.15 Mb PubMed search [3] [4]
Wikidata
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Structure

Dyskerin is an L-shaped protein consisting of approximately 514 amino acid residues, with a molecular weight of about 58 kilo-daltons.^[8] It belongs to the TruB family of pseudouridine synthase enzymes and forms the catalytic core of the H/ACA box snoRNP (small nucleolar ribonucleoprotein) complex. The DKC1 gene is located on the X chromosome, in a tail-to-tail orientation with the gene encoding palmitoylated erythrocyte membrane protein 1 (MPP1), and is transcribed in a telomere-to-centromere direction.^[7]

Function

The DKC1 gene encodes a core component of the H/ACA snoRNP complex, which also includes the NOLA1, NOLA2, and NOLA3 proteins. These proteins localize to the dense fibrillar components of nucleoli and to coiled (Cajal) bodies in the nucleus. The H/ACA snoRNPs catalyze pseudouridylation of rRNA and are essential for proper ribosome biogenesis. Depletion of any of the four core proteins impairs 18S rRNA production and pseudouridylation.^[7]

Beyond rRNA modification, dyskerin contributes to several other fundamental processes. It stabilizes the telomerase RNA component (TERC), thereby maintaining telomerase activity and ensuring telomere elongation and genomic stability.^[8] Dyskerin also participates in the assembly and maturation of ribosomal subunits by promoting correct folding and processing of pre-rRNA intermediates. In addition, it has been implicated in the regulation of pre-mRNA splicing, potentially through interactions with small Cajal body-specific RNAs (scaRNAs) that guide pseudouridylation of spliceosomal RNAs.^[8]

The human protein is homologous to Saccharomyces cerevisiae Cbf5p and Drosophila melanogaster Nop60B proteins, indicating strong evolutionary conservation.^[7]

Clinical significance

Mutations in DKC1 cause X-linked dyskeratosis congenita, a rare inherited disorder characterized by defective telomere maintenance, premature aging, bone marrow failure, and increased cancer susceptibility.^[5][6][7] Both nucleotide substitutions and trinucleotide repeat polymorphisms have been identified in this gene. The pathogenic variants typically impair dyskerin function, disrupting rRNA modification and telomerase RNA stability, leading to the disease phenotype.

Mutations in DKC1 are also associated with Hoyeraal-Hreidarsson syndrome.^[9]