Dyskerin

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
Gene location (Human) Chr. X chromosome (human) Band Xq28 Start 154,762,742 bp End 154,777,689 bp
Gene location (Mouse) Chr. X chromosome (mouse) Band X|X A7.3 Start 74,139,460 bp End 74,153,383 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in secondary oocyte sural nerve hair follicle tibia pancreatic ductal cell Achilles tendon body of pancreas islet of Langerhans palpebral conjunctiva rectum Top expressed in hand primitive streak secondary oocyte abdominal wall blastocyst yolk sac cumulus cell morula hair follicle maxillary prominence 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
Wikidata
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H/ACA ribonucleoprotein complex subunit 4 is a protein that in humans is encoded by the gene DKC1.

Dyskerin is a pseudouridine synthase enzyme which is part of the TruB family of enzymes. Dyskerin is an L-shaped protein of 514 residues and a molecular weight of about 58 kilo-daltons. Dyskerin is essential for the activity of telomerase by accumulating telomerase RNA component (TERC).

This gene is a member of the H/ACA snoRNPs (small nucleolar ribonucleoproteins) gene family. snoRNPs are involved in various aspects of rRNA processing and modification and have been classified into two families: C/D and H/ACA. The H/ACA snoRNPs also include the NOLA1, 2 and 3 proteins. The protein encoded by this gene and the three NOLA proteins localize to the dense fibrillar components of nucleoli and to coiled (Cajal) bodies in the nucleus. Both 18S rRNA production and rRNA pseudouridylation are impaired if any one of the four proteins is depleted. The protein encoded by this gene is related to the Saccharomyces cerevisiae Cbf5p and Drosophila melanogaster Nop60B proteins. The gene lies in a tail-to-tail orientation with the palmitoylated erythrocyte membrane protein (MPP1) gene and is transcribed in a telomere to centromere direction. Both nucleotide substitutions and single trinucleotide repeat polymorphisms have been found in this gene. Mutations in this gene cause X-linked dyskeratosis congenita.

Clinical significance

Mutations in DKC1 are associated to Hoyeraal-Hreidarsson syndrome.

Further reading

• Marrone A, Dokal I (2004). "Dyskeratosis congenita: molecular insights into telomerase function, ageing and cancer". Expert Reviews in Molecular Medicine. 6 (26): 1–23. doi:10.1017/S1462399404008671. PMID 15613268. S2CID 38163343.
• Yamaguchi H (2007). "Mutations of telomerase complex genes linked to bone marrow failures". Journal of Nippon Medical School. 74 (3): 202–9. doi:10.1272/jnms.74.202. PMID 17625368.
• Aalfs CM, van den Berg H, Barth PG, Hennekam RC (1995). "The Hoyeraal-Hreidarsson syndrome: the fourth case of a separate entity with prenatal growth retardation, progressive pancytopenia and cerebellar hypoplasia". Eur. J. Pediatr. 154 (4): 304–8. doi:10.1007/BF01957367. PMID 7607282. S2CID 441225.
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Devriendt K, Matthijs G, Legius E, et al. (1997). "Skewed X-chromosome inactivation in female carriers of dyskeratosis congenita". Am. J. Hum. Genet. 60 (3): 581–7. PMC 1712491. PMID 9042917.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• McGrath JA (1999). "Dyskeratosis congenita: new clinical and molecular insights into ribosome function". Lancet. 353 (9160): 1204–5. doi:10.1016/S0140-6736(99)00011-2. PMID 10217077. S2CID 490860.
• Knight SW, Heiss NS, Vulliamy TJ, et al. (1999). "X-linked dyskeratosis congenita is predominantly caused by missense mutations in the DKC1 gene". Am. J. Hum. Genet. 65 (1): 50–8. doi:10.1086/302446. PMC 1378074. PMID 10364516.
• Vulliamy TJ, Knight SW, Heiss NS, et al. (1999). "Dyskeratosis congenita caused by a 3' deletion: germline and somatic mosaicism in a female carrier". Blood. 94 (4): 1254–60. doi:10.1182/blood.V94.4.1254. PMID 10438713.
• Heiss NS, Girod A, Salowsky R, et al. (2000). "Dyskerin localizes to the nucleolus and its mislocalization is unlikely to play a role in the pathogenesis of dyskeratosis congenita". Hum. Mol. Genet. 8 (13): 2515–24. doi:10.1093/hmg/8.13.2515. PMID 10556300.
• Knight SW, Heiss NS, Vulliamy TJ, et al. (2000). "Unexplained aplastic anaemia, immunodeficiency, and cerebellar hypoplasia (Hoyeraal-Hreidarsson syndrome) due to mutations in the dyskeratosis congenita gene, DKC1". Br. J. Haematol. 107 (2): 335–9. doi:10.1046/j.1365-2141.1999.01690.x. PMID 10583221. S2CID 23750791.
• Mitchell JR, Wood E, Collins K (1999). "A telomerase component is defective in the human disease dyskeratosis congenita". Nature. 402 (6761): 551–5. Bibcode:1999Natur.402..551M. doi:10.1038/990141. PMID 10591218. S2CID 4430482.
• Yaghmai R, Kimyai-Asadi A, Rostamiani K, et al. (2000). "Overlap of dyskeratosis congenita with the Hoyeraal-Hreidarsson syndrome". J. Pediatr. 136 (3): 390–3. doi:10.1067/mpd.2000.104295. PMID 10700698.
• Heiss NS, Bächner D, Salowsky R, et al. (2000). "Gene structure and expression of the mouse dyskeratosis congenita gene, dkc1". Genomics. 67 (2): 153–63. doi:10.1006/geno.2000.6227. PMID 10903840.
• Pogacić V, Dragon F, Filipowicz W (2000). "Human H/ACA Small Nucleolar RNPs and Telomerase Share Evolutionarily Conserved Proteins NHP2 and NOP10". Mol. Cell. Biol. 20 (23): 9028–40. doi:10.1128/MCB.20.23.9028-9040.2000. PMC 86556. PMID 11074001.
• Hartley JL, Temple GF, Brasch MA (2001). "DNA Cloning Using In Vitro Site-Specific Recombination". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
• Simpson JC, Wellenreuther R, Poustka A, et al. (2001). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Rep. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614.
• Knight SW, Vulliamy TJ, Morgan B, et al. (2001). "Identification of novel DKC1 mutations in patients with dyskeratosis congenita: implications for pathophysiology and diagnosis". Hum. Genet. 108 (4): 299–303. doi:10.1007/s004390100494. PMID 11379875. S2CID 23829134.

External links

• GeneReviews/NCBI/NIH/UW entry on Dyskeratosis Congenita