Dyskerin

H/ACA ribonucleoprotein complex subunit 4 is a protein that in humans is encoded by the gene DKC1.[5][6][7]

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)[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 75,095,854 bp[2] End 75,109,777 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • telomerase activity • pseudouridine synthase activity • isomerase activity • box H/ACA snoRNA binding • GO:0001948 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 • cell 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 snoRNA 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 • GO:0016547 RNA modification • cellular proliferation • mRNA pseudouridine synthesis • box H/ACA snoRNA 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: 75.1 – 75.11 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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.[7]

Clinical significance

Mutations in DKC1 are associated to Hoyeraal-Hreidarsson syndrome.[8]

References

1. GRCh38: Ensembl release 89: ENSG00000130826 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000031403 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Heiss NS, Knight SW, Vulliamy TJ, Klauck SM, Wiemann S, Mason PJ, Poustka A, Dokal I (May 1998). "X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions". Nat Genet. 19 (1): 32–8. doi:10.1038/ng0598-32. PMID 9590285.
6. Hassock S, Vetrie D, Giannelli F (Mar 1999). "Mapping and characterization of the X-linked dyskeratosis congenita (DKC) gene". Genomics. 55 (1): 21–7. doi:10.1006/geno.1998.5600. PMID 9888995.
7. "Entrez Gene: DKC1 dyskeratosis congenita 1, dyskerin".
8. Lim, B. C.; Yoo, S. K.; Lee, S; Shin, J. Y.; Hwang, H; Chae, J. H.; Hwang, Y. S.; Seo, J. S.; Kim, J. I.; Kim, K. J. (2014). "Hoyeraal-Hreidarsson syndrome with a DKC1 mutation identified by whole-exome sequencing". Gene. 546 (2): 425–9. doi:10.1016/j.gene.2014.06.011. PMID 24914498.

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.
• 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.
• 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.
• 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. 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.
• Mitchell JR, Wood E, Collins K (1999). "A telomerase component is defective in the human disease dyskeratosis congenita". Nature. 402 (6761): 551–5. doi:10.1038/990141. PMID 10591218.
• 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.

External links

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