{{short description|Protein}} {{Redirect|DKC1|the 1994 video game|Donkey Kong Country}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox gene}} '''H/ACA ribonucleoprotein complex subunit 4''' is a protein that in humans is encoded by the ''DKC1'' gene.<ref name="Heiss_1998">{{cite journal | vauthors = Heiss NS, Knight SW, Vulliamy TJ, Klauck SM, Wiemann S, Mason PJ, Poustka A, Dokal I | title = X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions | journal = Nature Genetics | volume = 19 | issue = 1 | pages = 32–38 | date = May 1998 | pmid = 9590285 | doi = 10.1038/ng0598-32 | s2cid = 205342127 }}</ref><ref name="Hassock_1999">{{cite journal | vauthors = Hassock S, Vetrie D, Giannelli F | title = Mapping and characterization of the X-linked dyskeratosis congenita (DKC) gene | journal = Genomics | volume = 55 | issue = 1 | pages = 21–27 | date = January 1999 | pmid = 9888995 | doi = 10.1006/geno.1998.5600 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: DKC1 dyskeratosis congenita 1, dyskerin | url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=1736 }}</ref> The encoded protein, known as '''dyskerin''', is a highly conserved nucleolar enzyme that plays key roles in rRNA modification, telomerase function, and ribosome biogenesis.
== Structure == Dyskerin is an L-shaped protein consisting of approximately 514 amino acid residues, with a molecular weight of about 58 kilo-daltons.<ref name="Garus_2021">{{cite journal | vauthors = Garus A, Autexier C | title = Dyskerin: an essential pseudouridine synthase with multifaceted roles in ribosome biogenesis, splicing, and telomere maintenance | journal = RNA | volume = 27 | issue = 12 | pages = 1441–1458 | date = December 2021 | pmid = 34556550 | pmc = 8594475 | doi = 10.1261/rna.078953.121 }}</ref> 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.<ref name="entrez" />
== 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.<ref name="entrez" />
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.<ref name="Garus_2021" /> 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.<ref name="Garus_2021" />
The human protein is homologous to ''Saccharomyces cerevisiae'' Cbf5p and ''Drosophila melanogaster'' Nop60B proteins, indicating strong evolutionary conservation.<ref name="entrez" />
== 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.<ref name="Heiss_1998" /><ref name="Hassock_1999" /><ref name="entrez" /> 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.<ref>{{cite journal | vauthors = Lim BC, Yoo SK, Lee S, Shin JY, Hwang H, Chae JH, Hwang YS, Seo JS, Kim JI, Kim KJ | title = Hoyeraal-Hreidarsson syndrome with a DKC1 mutation identified by whole-exome sequencing | journal = Gene | volume = 546 | issue = 2 | pages = 425–429 | date = August 2014 | pmid = 24914498 | doi = 10.1016/j.gene.2014.06.011 }}</ref>
== References == {{reflist}}
== Further reading == {{refbegin | 2}} * {{cite journal | vauthors = Marrone A, Dokal I | title = Dyskeratosis congenita: molecular insights into telomerase function, ageing and cancer | journal = Expert Reviews in Molecular Medicine | volume = 6 | issue = 26 | pages = 1–23 | date = December 2004 | pmid = 15613268 | doi = 10.1017/S1462399404008671 | s2cid = 38163343 }} * {{cite journal | vauthors = Yamaguchi H | title = Mutations of telomerase complex genes linked to bone marrow failures | journal = Journal of Nippon Medical School = Nippon Ika Daigaku Zasshi | volume = 74 | issue = 3 | pages = 202–209 | date = June 2007 | pmid = 17625368 | doi = 10.1272/jnms.74.202 | doi-access = free }} * {{cite journal | vauthors = Aalfs CM, van den Berg H, Barth PG, Hennekam RC | title = The Hoyeraal-Hreidarsson syndrome: the fourth case of a separate entity with prenatal growth retardation, progressive pancytopenia and cerebellar hypoplasia | journal = European Journal of Pediatrics | volume = 154 | issue = 4 | pages = 304–308 | date = April 1995 | pmid = 7607282 | doi = 10.1007/BF01957367 | s2cid = 441225 }} * {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–174 | date = January 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }} * {{cite journal | vauthors = Devriendt K, Matthijs G, Legius E, Schollen E, Blockmans D, van Geet C, Degreef H, Cassiman JJ, Fryns JP | title = Skewed X-chromosome inactivation in female carriers of dyskeratosis congenita | journal = American Journal of Human Genetics | volume = 60 | issue = 3 | pages = 581–587 | date = March 1997 | pmid = 9042917 | pmc = 1712491 }} * {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–156 | date = October 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }} * {{cite journal | vauthors = McGrath JA | title = Dyskeratosis congenita: new clinical and molecular insights into ribosome function | journal = Lancet | volume = 353 | issue = 9160 | pages = 1204–1205 | date = April 1999 | pmid = 10217077 | doi = 10.1016/S0140-6736(99)00011-2 | s2cid = 490860 }} * {{cite journal | vauthors = Knight SW, Heiss NS, Vulliamy TJ, Greschner S, Stavrides G, Pai GS, Lestringant G, Varma N, Mason PJ, Dokal I, Poustka A | title = X-linked dyskeratosis congenita is predominantly caused by missense mutations in the DKC1 gene | journal = American Journal of Human Genetics | volume = 65 | issue = 1 | pages = 50–58 | date = July 1999 | pmid = 10364516 | pmc = 1378074 | doi = 10.1086/302446 }} * {{cite journal | vauthors = Vulliamy TJ, Knight SW, Heiss NS, Smith OP, Poustka A, Dokal I, Mason PJ | title = Dyskeratosis congenita caused by a 3' deletion: germline and somatic mosaicism in a female carrier | journal = Blood | volume = 94 | issue = 4 | pages = 1254–1260 | date = August 1999 | pmid = 10438713 | doi = 10.1182/blood.V94.4.1254 }} * {{cite journal | vauthors = Heiss NS, Girod A, Salowsky R, Wiemann S, Pepperkok R, Poustka A | title = Dyskerin localizes to the nucleolus and its mislocalization is unlikely to play a role in the pathogenesis of dyskeratosis congenita | journal = Human Molecular Genetics | volume = 8 | issue = 13 | pages = 2515–2524 | date = December 1999 | pmid = 10556300 | doi = 10.1093/hmg/8.13.2515 }} * {{cite journal | vauthors = Knight SW, Heiss NS, Vulliamy TJ, Aalfs CM, McMahon C, Richmond P, Jones A, Hennekam RC, Poustka A, Mason PJ, Dokal I | title = Unexplained aplastic anaemia, immunodeficiency, and cerebellar hypoplasia (Hoyeraal-Hreidarsson syndrome) due to mutations in the dyskeratosis congenita gene, DKC1 | journal = British Journal of Haematology | volume = 107 | issue = 2 | pages = 335–339 | date = November 1999 | pmid = 10583221 | doi = 10.1046/j.1365-2141.1999.01690.x | s2cid = 23750791 }} * {{cite journal | vauthors = Mitchell JR, Wood E, Collins K | title = A telomerase component is defective in the human disease dyskeratosis congenita | journal = Nature | volume = 402 | issue = 6761 | pages = 551–555 | date = December 1999 | pmid = 10591218 | doi = 10.1038/990141 | s2cid = 4430482 | bibcode = 1999Natur.402..551M }} * {{cite journal | vauthors = Yaghmai R, Kimyai-Asadi A, Rostamiani K, Heiss NS, Poustka A, Eyaid W, Bodurtha J, Nousari HC, Hamosh A, Metzenberg A | title = Overlap of dyskeratosis congenita with the Hoyeraal-Hreidarsson syndrome | journal = The Journal of Pediatrics | volume = 136 | issue = 3 | pages = 390–393 | date = March 2000 | pmid = 10700698 | doi = 10.1067/mpd.2000.104295 | doi-access = free }} * {{cite journal | vauthors = Heiss NS, Bächner D, Salowsky R, Kolb A, Kioschis P, Poustka A | title = Gene structure and expression of the mouse dyskeratosis congenita gene, dkc1 | journal = Genomics | volume = 67 | issue = 2 | pages = 153–163 | date = July 2000 | pmid = 10903840 | doi = 10.1006/geno.2000.6227 }} * {{cite journal | vauthors = Pogacić V, Dragon F, Filipowicz W | title = Human H/ACA small nucleolar RNPs and telomerase share evolutionarily conserved proteins NHP2 and NOP10 | journal = Molecular and Cellular Biology | volume = 20 | issue = 23 | pages = 9028–9040 | date = December 2000 | pmid = 11074001 | pmc = 86556 | doi = 10.1128/MCB.20.23.9028-9040.2000 }} * {{cite journal | vauthors = Hartley JL, Temple GF, Brasch MA | title = DNA cloning using in vitro site-specific recombination | journal = Genome Research | volume = 10 | issue = 11 | pages = 1788–1795 | date = November 2000 | pmid = 11076863 | pmc = 310948 | doi = 10.1101/gr.143000 }} * {{cite journal | vauthors = Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S | title = Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing | journal = EMBO Reports | volume = 1 | issue = 3 | pages = 287–292 | date = September 2000 | pmid = 11256614 | pmc = 1083732 | doi = 10.1093/embo-reports/kvd058 }} * {{cite journal | vauthors = Knight SW, Vulliamy TJ, Morgan B, Devriendt K, Mason PJ, Dokal I | title = Identification of novel DKC1 mutations in patients with dyskeratosis congenita: implications for pathophysiology and diagnosis | journal = Human Genetics | volume = 108 | issue = 4 | pages = 299–303 | date = April 2001 | pmid = 11379875 | doi = 10.1007/s004390100494 | s2cid = 23829134 }} {{refend}}
== External links == * [https://www.ncbi.nlm.nih.gov/books/NBK22301/ GeneReviews/NCBI/NIH/UW entry on Dyskeratosis Congenita]
{{DNA replication}}
Category:Telomere-related genes Category:Telomere-related proteins Category:Long stubs with short prose
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