ID DKC1_HUMAN Reviewed; 514 AA. AC O60832; F5BSB3; O43845; Q96G67; Q9Y505; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 27-MAR-2024, entry version 236. DE RecName: Full=H/ACA ribonucleoprotein complex subunit DKC1; DE EC=5.4.99.- {ECO:0000305|PubMed:25219674}; DE AltName: Full=CBF5 homolog; DE AltName: Full=Dyskerin; DE AltName: Full=Nopp140-associated protein of 57 kDa; DE AltName: Full=Nucleolar protein NAP57; DE AltName: Full=Nucleolar protein family A member 4; DE AltName: Full=snoRNP protein DKC1; GN Name=DKC1 {ECO:0000312|HGNC:HGNC:2890}; Synonyms=NOLA4; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INVOLVEMENT IN DKCX, AND VARIANTS RP DKCX VAL-36; LEU-37 DEL; ARG-40; TYR-72 AND GLU-402. RX PubMed=9590285; DOI=10.1038/ng0598-32; RA Heiss N.S., Knight S.W., Vulliamy T.J., Klauck S.M., Wiemann S., RA Mason P.J., Poustka A., Dokal I.; RT "X-linked dyskeratosis congenita is caused by mutations in a highly RT conserved gene with putative nucleolar functions."; RL Nat. Genet. 19:32-38(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS DKCX VAL-2; GLU-39; RP LYS-41; THR-65; ALA-66; VAL-321; ILE-350; THR-350; VAL-353 AND ARG-402. RX PubMed=10364516; DOI=10.1086/302446; RA Knight S.W., Heiss N.S., Vulliamy T.J., Greschner S., Stavrides G., RA Pai G.S., Lestringant G., Varma N., Mason P.J., Dokal I., Poustka A.; RT "X-linked dyskeratosis congenita is predominantly caused by missense RT mutations in the DKC1 gene."; RL Am. J. Hum. Genet. 65:50-58(1999). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1). RX PubMed=9888995; DOI=10.1006/geno.1998.5600; RA Hassock S., Vetrie D., Giannelli F.; RT "Mapping and characterization of the X-linked dyskeratosis congenita (DKC) RT gene."; RL Genomics 55:21-27(1999). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Jiang W., Clifford J., Koltin Y.; RT "A highly conserved nucleolar protein from human interacts with a HMG-like RT protein."; RL Submitted (MAY-1996) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), SUBCELLULAR LOCATION (ISOFORM 3), RP AND FUNCTION (ISOFORM 3). RX PubMed=21820037; DOI=10.1016/j.bbagen.2011.07.012; RA Angrisani A., Turano M., Paparo L., Di Mauro C., Furia M.; RT "A new human dyskerin isoform with cytoplasmic localization."; RL Biochim. Biophys. Acta 1810:1361-1368(2011). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C., RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., RA Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Uterus; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP PROTEIN SEQUENCE OF 2-11; 118-127; 159-191; 284-291; 303-322 AND 426-443, RP CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND IDENTIFICATION RP BY MASS SPECTROMETRY. RC TISSUE=Cervix carcinoma; RA Bienvenut W.V.; RL Submitted (OCT-2004) to UniProtKB. RN [9] RP SUBCELLULAR LOCATION, AND DOMAIN NUCLEOLAR LOCALIZATION. RX PubMed=10556300; DOI=10.1093/hmg/8.13.2515; RA Heiss N.S., Girod A., Salowsky R., Wiemann S., Pepperkok R., Poustka A.; RT "Dyskerin localizes to the nucleolus and its mislocalization is unlikely to RT play a role in the pathogenesis of dyskeratosis congenita."; RL Hum. Mol. Genet. 8:2515-2524(1999). RN [10] RP SUBCELLULAR LOCATION, AND ASSOCIATION WITH TELOMERASE. RX PubMed=10591218; DOI=10.1038/990141; RA Mitchell J.R., Wood E., Collins K.; RT "A telomerase component is defective in the human disease dyskeratosis RT congenita."; RL Nature 402:551-555(1999). RN [11] RP TISSUE SPECIFICITY. RX PubMed=10903840; DOI=10.1006/geno.2000.6227; RA Heiss N.S., Baechner D., Salowsky R., Kolb A., Kioschis P., Poustka A.; RT "Gene structure and expression of the mouse dyskeratosis congenita gene, RT dkc1."; RL Genomics 67:153-163(2000). RN [12] RP INTERACTION WITH NHP2. RX PubMed=11074001; DOI=10.1128/mcb.20.23.9028-9040.2000; RA Pogacic V., Dragon F., Filipowicz W.; RT "Human H/ACA small nucleolar RNPs and telomerase share evolutionarily RT conserved proteins NHP2 and NOP10."; RL Mol. Cell. Biol. 20:9028-9040(2000). RN [13] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=12429849; DOI=10.1091/mbc.e02-05-0271; RA Scherl A., Coute Y., Deon C., Calle A., Kindbeiter K., Sanchez J.-C., RA Greco A., Hochstrasser D.F., Diaz J.-J.; RT "Functional proteomic analysis of human nucleolus."; RL Mol. Biol. Cell 13:4100-4109(2002). RN [14] RP CHARACTERIZATION OF THE H/ACA SNORNP COMPLEX. RX PubMed=15044956; DOI=10.1038/sj.emboj.7600181; RA Wang C., Meier U.T.; RT "Architecture and assembly of mammalian H/ACA small nucleolar and RT telomerase ribonucleoproteins."; RL EMBO J. 23:1857-1867(2004). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21 AND SER-513, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [16] RP INTERACTION WITH NAF1. RX PubMed=16618814; DOI=10.1083/jcb.200601105; RA Darzacq X., Kittur N., Roy S., Shav-Tal Y., Singer R.H., Meier U.T.; RT "Stepwise RNP assembly at the site of H/ACA RNA transcription in human RT cells."; RL J. Cell Biol. 173:207-218(2006). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-494, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein phosphorylation RT analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [18] RP INTERACTION WITH NAF1. RX PubMed=16601202; DOI=10.1261/rna.2344106; RA Hoareau-Aveilla C., Bonoli M., Caizergues-Ferrer M., Henry Y.; RT "hNaf1 is required for accumulation of human box H/ACA snoRNPs, scaRNPs, RT and telomerase."; RL RNA 12:832-840(2006). RN [19] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Prostate cancer; RX PubMed=17487921; DOI=10.1002/elps.200600782; RA Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S.; RT "Toward a global characterization of the phosphoproteome in prostate cancer RT cells: identification of phosphoproteins in the LNCaP cell line."; RL Electrophoresis 28:2027-2034(2007). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21; SER-485 AND SER-494, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [22] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=18318008; DOI=10.1002/pmic.200700884; RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., RA Zou H., Gu J.; RT "Large-scale phosphoproteome analysis of human liver tissue by enrichment RT and fractionation of phosphopeptides with strong anion exchange RT chromatography."; RL Proteomics 8:1346-1361(2008). RN [23] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [24] RP INTERACTION WITH SHQ1, CHARACTERIZATION OF VARIANTS DKCX ALA-66; ILE-350; RP THR-350 AND VAL-353, CHARACTERIZATION OF VARIANTS HHS MET-49 AND GLY-121, RP AND MUTAGENESIS OF ALA-353. RX PubMed=19734544; DOI=10.1093/hmg/ddp416; RA Grozdanov P.N., Fernandez-Fuentes N., Fiser A., Meier U.T.; RT "Pathogenic NAP57 mutations decrease ribonucleoprotein assembly in RT dyskeratosis congenita."; RL Hum. Mol. Genet. 18:4546-4551(2009). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-513, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [26] RP INTERACTION WITH SHQ1. RX PubMed=19383767; DOI=10.1261/rna.1532109; RA Grozdanov P.N., Roy S., Kittur N., Meier U.T.; RT "SHQ1 is required prior to NAF1 for assembly of H/ACA small nucleolar and RT telomerase RNPs."; RL RNA 15:1188-1197(2009). RN [27] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21; SER-485 AND SER-494, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [28] RP IDENTIFICATION IN THE TELOMERASE HOLOENZYME COMPLEX, AND FUNCTION. RX PubMed=19179534; DOI=10.1126/science.1165357; RA Venteicher A.S., Abreu E.B., Meng Z., McCann K.E., Terns R.M., RA Veenstra T.D., Terns M.P., Artandi S.E.; RT "A human telomerase holoenzyme protein required for Cajal body localization RT and telomere synthesis."; RL Science 323:644-648(2009). RN [29] RP IDENTIFICATION IN THE TELOMERASE HOLOENZYME COMPLEX. RX PubMed=20351177; DOI=10.1128/mcb.00151-10; RA Egan E.D., Collins K.; RT "Specificity and stoichiometry of subunit interactions in the human RT telomerase holoenzyme assembled in vivo."; RL Mol. Cell. Biol. 30:2775-2786(2010). RN [30] RP INVOLVEMENT IN HHS, AND VARIANTS HHS MET-49 AND GLY-121. RX PubMed=10583221; DOI=10.1046/j.1365-2141.1999.01690.x; RA Knight S.W., Heiss N.S., Vulliamy T.J., Aalfs C.M., McMahon C., RA Richmond P., Jones A., Hennekam R.C.M., Poustka A., Mason P.J., Dokal I.; RT "Unexplained aplastic anaemia, immunodeficiency, and cerebellar hypoplasia RT (Hoyeraal-Hreidarsson syndrome) due to mutations in the dyskeratosis RT congenita gene, DKC1."; RL Br. J. Haematol. 107:335-339(1999). RN [31] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21; SER-451; SER-453; RP SER-485; SER-494 AND SER-513, AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [32] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [33] RP INTERACTION WITH DHX36. RX PubMed=21846770; DOI=10.1093/nar/gkr630; RA Lattmann S., Stadler M.B., Vaughn J.P., Akman S.A., Nagamine Y.; RT "The DEAH-box RNA helicase RHAU binds an intramolecular RNA G-quadruplex in RT TERC and associates with telomerase holoenzyme."; RL Nucleic Acids Res. 39:9390-9404(2011). RN [34] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21; SER-451; SER-453; RP SER-455; SER-485; SER-494 AND SER-513, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [35] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [36] RP INTERACTION WITH HMBOX1. RX PubMed=23685356; DOI=10.1038/emboj.2013.105; RA Kappei D., Butter F., Benda C., Scheibe M., Draskovic I., Stevense M., RA Novo C.L., Basquin C., Araki M., Araki K., Krastev D.B., Kittler R., RA Jessberger R., Londono-Vallejo J.A., Mann M., Buchholz F.; RT "HOT1 is a mammalian direct telomere repeat-binding protein contributing to RT telomerase recruitment."; RL EMBO J. 32:1681-1701(2013). RN [37] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-387; SER-451; SER-453; RP SER-485; SER-494 AND SER-513, AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [38] RP FUNCTION, CATALYTIC ACTIVITY, AND INVOLVEMENT IN DKCX. RX PubMed=25219674; DOI=10.1016/j.cell.2014.08.028; RA Schwartz S., Bernstein D.A., Mumbach M.R., Jovanovic M., Herbst R.H., RA Leon-Ricardo B.X., Engreitz J.M., Guttman M., Satija R., Lander E.S., RA Fink G., Regev A.; RT "Transcriptome-wide mapping reveals widespread dynamic-regulated RT pseudouridylation of ncRNA and mRNA."; RL Cell 159:148-162(2014). RN [39] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-494, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [40] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-413, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). RN [41] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-413, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25114211; DOI=10.1073/pnas.1413825111; RA Impens F., Radoshevich L., Cossart P., Ribet D.; RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by RT external stimuli."; RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014). RN [42] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-413, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033; RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V., RA Vertegaal A.C.; RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage."; RL Cell Rep. 10:1778-1791(2015). RN [43] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-413, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25755297; DOI=10.1074/mcp.o114.044792; RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V., RA Vertegaal A.C.; RT "System-wide analysis of SUMOylation dynamics in response to replication RT stress reveals novel small ubiquitin-like modified target proteins and RT acceptor lysines relevant for genome stability."; RL Mol. Cell. Proteomics 14:1419-1434(2015). RN [44] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-20; LYS-39; LYS-43; LYS-191; RP LYS-394; LYS-413; LYS-424; LYS-433 AND LYS-467, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [45] RP STRUCTURE BY ELECTRON MICROSCOPY (7.7 ANGSTROMS) OF THE TELOMERASE RP HOLOENZYME COMPLEX. RX PubMed=29695869; DOI=10.1038/s41586-018-0062-x; RA Nguyen T.H.D., Tam J., Wu R.A., Greber B.J., Toso D., Nogales E., RA Collins K.; RT "Cryo-EM structure of substrate-bound human telomerase holoenzyme."; RL Nature 557:190-195(2018). RN [46] RP VARIANT HHS THR-38. RX PubMed=12437656; DOI=10.1046/j.1365-2141.2002.03822.x; RA Cossu F., Vulliamy T.J., Marrone A., Badiali M., Cao A., Dokal I.; RT "A novel DKC1 mutation, severe combined immunodeficiency (T+B-NK-SCID) and RT bone marrow transplantation in an infant with Hoyeraal-Hreidarsson RT syndrome."; RL Br. J. Haematol. 119:765-768(2002). RN [47] RP VARIANTS DKCX VAL-353 AND LEU-409. RX PubMed=15304085; DOI=10.1111/j.0022-202x.2004.23228.x; RA Ding Y.G., Zhu T.S., Jiang W., Yang Y., Bu D.F., Tu P., Zhu X.J., RA Wang B.X.; RT "Identification of a novel mutation and a de novo mutation in DKC1 in two RT Chinese pedigrees with Dyskeratosis congenita."; RL J. Invest. Dermatol. 123:470-473(2004). RN [48] RP VARIANT DKCX PHE-72. RX PubMed=17417794; DOI=10.1002/pbc.21203; RA Hamidah A., Rashid R.A., Jamal R., Zhao M., Kanegane H.; RT "X-linked dyskeratosis congenita in Malaysia."; RL Pediatr. Blood Cancer 50:432-432(2008). RN [49] RP VARIANT DKCX SER-56. RX PubMed=18802941; DOI=10.1002/pbc.21733; RA Kurnikova M., Shagina I., Khachatryan L., Schagina O., Maschan M., RA Shagin D.; RT "Identification of a novel mutation in DKC1 in dyskeratosis congenita."; RL Pediatr. Blood Cancer 52:135-137(2009). RN [50] RP VARIANTS DKCX PHE-317 AND GLN-322. RX PubMed=19879169; DOI=10.1016/j.bcmd.2009.10.005; RA Rostamiani K., Klauck S.M., Heiss N., Poustka A., Khaleghi M., Rosales R., RA Metzenberg A.B.; RT "Novel mutations of the DKC1 gene in individuals affected with dyskeratosis RT congenita."; RL Blood Cells Mol. Dis. 44:88-88(2010). RN [51] RP VARIANTS DKCX LEU-37 DEL AND VAL-54, AND CHARACTERIZATION OF VARIANTS DKCX RP LEU-37 DEL AND VAL-54. RX PubMed=21602826; DOI=10.1038/nature10084; RA Batista L.F., Pech M.F., Zhong F.L., Nguyen H.N., Xie K.T., Zaug A.J., RA Crary S.M., Choi J., Sebastiano V., Cherry A., Giri N., Wernig M., RA Alter B.P., Cech T.R., Savage S.A., Reijo Pera R.A., Artandi S.E.; RT "Telomere shortening and loss of self-renewal in dyskeratosis congenita RT induced pluripotent stem cells."; RL Nature 474:399-402(2011). RN [52] RP VARIANT HHS MET-49. RX PubMed=24914498; DOI=10.1016/j.gene.2014.06.011; RA Lim B.C., Yoo S.K., Lee S., Shin J.Y., Hwang H., Chae J.H., Hwang Y.S., RA Seo J.S., Kim J.I., Kim K.J.; RT "Hoyeraal-Hreidarsson syndrome with a DKC1 mutation identified by whole- RT exome sequencing."; RL Gene 546:425-429(2014). RN [53] RP VARIANT CHINE1 LYS-206, INVOLVEMENT IN CHINE1, CHARACTERIZATION OF VARIANT RP CHINE1 LYS-206, AND FUNCTION. RX PubMed=32554502; DOI=10.1073/pnas.2002328117; RA Balogh E., Chandler J.C., Varga M., Tahoun M., Menyhard D.K., Schay G., RA Goncalves T., Hamar R., Legradi R., Szekeres A., Gribouval O., Kleta R., RA Stanescu H., Bockenhauer D., Kerti A., Williams H., Kinsler V., Di W.L., RA Curtis D., Kolatsi-Joannou M., Hammid H., Szocs A., Perczel K., Maka E., RA Toldi G., Sava F., Arrondel C., Kardos M., Fintha A., Hossain A., RA D'Arco F., Kaliakatsos M., Koeglmeier J., Mifsud W., Moosajee M., Faro A., RA Javorszky E., Rudas G., Saied M.H., Marzouk S., Kelen K., Goetze J., RA Reusz G., Tulassay T., Dragon F., Mollet G., Motameny S., Thiele H., RA Dorval G., Nuernberg P., Perczel A., Szabo A.J., Long D.A., Tomita K., RA Antignac C., Waters A.M., Tory K.; RT "Pseudouridylation defect due to DKC1 and NOP10 mutations causes nephrotic RT syndrome with cataracts, hearing impairment, and enterocolitis."; RL Proc. Natl. Acad. Sci. U.S.A. 117:15137-15147(2020). CC -!- FUNCTION: [Isoform 1]: Catalytic subunit of H/ACA small nucleolar CC ribonucleoprotein (H/ACA snoRNP) complex, which catalyzes CC pseudouridylation of rRNA (PubMed:25219674, PubMed:32554502). This CC involves the isomerization of uridine such that the ribose is CC subsequently attached to C5, instead of the normal N1 CC (PubMed:25219674). Each rRNA can contain up to 100 pseudouridine CC ('psi') residues, which may serve to stabilize the conformation of CC rRNAs. Required for ribosome biogenesis and telomere maintenance CC (PubMed:19179534, PubMed:25219674). Also required for correct CC processing or intranuclear trafficking of TERC, the RNA component of CC the telomerase reverse transcriptase (TERT) holoenzyme CC (PubMed:19179534). {ECO:0000269|PubMed:19179534, CC ECO:0000269|PubMed:25219674, ECO:0000269|PubMed:32554502}. CC -!- FUNCTION: [Isoform 3]: Promotes cell to cell and cell to substratum CC adhesion, increases the cell proliferation rate and leads to CC cytokeratin hyper-expression. {ECO:0000269|PubMed:21820037}. CC -!- CATALYTIC ACTIVITY: CC Reaction=uridine in 5S rRNA = pseudouridine in 5S rRNA; CC Xref=Rhea:RHEA:47036, Rhea:RHEA-COMP:11730, Rhea:RHEA-COMP:11731, CC ChEBI:CHEBI:65314, ChEBI:CHEBI:65315; CC Evidence={ECO:0000305|PubMed:25219674}; CC -!- SUBUNIT: Part of the H/ACA small nucleolar ribonucleoprotein (H/ACA CC snoRNP) complex, which contains NHP2/NOLA2, GAR1/NOLA1, NOP10/NOLA3, CC and DKC1/NOLA4, which is presumed to be the catalytic subunit CC (PubMed:15044956). The complex contains a stable core formed by binding CC of one or two NOP10-DKC1 heterodimers to NHP2; GAR1 subsequently binds CC to this core via DKC1 (PubMed:15044956). The complex binds a box H/ACA CC small nucleolar RNA (snoRNA), which may target the specific site of CC modification within the RNA substrate (PubMed:15044956). During CC assembly, the complex contains NAF1 instead of GAR1/NOLA1 CC (PubMed:16601202, PubMed:16618814). The complex also interacts with CC TERC, which contains a 3'-terminal domain related to the box H/ACA CC snoRNAs. Specific interactions with snoRNAs or TERC are mediated by CC GAR1 and NHP2. Associates with NOLC1/NOPP140 (PubMed:15044956). H/ACA CC snoRNPs interact with the SMN complex, consisting of SMN1 or SMN2, CC GEMIN2/SIP1, DDX20/GEMIN3, and GEMIN4. This is mediated by interaction CC between GAR1 and SMN1 or SMN2. The SMN complex may be required for CC correct assembly of the H/ACA snoRNP complex (PubMed:15044956). CC Component of the telomerase holoenzyme complex composed of one molecule CC of TERT, one molecule of WRAP53/TCAB1, two molecules of H/ACA CC ribonucleoprotein complex subunits DKC1, NOP10, NHP2 and GAR1, and a CC telomerase RNA template component (TERC) (PubMed:11074001, CC PubMed:19179534, PubMed:20351177, PubMed:29695869). The telomerase CC holoenzyme complex is associated with TEP1, SMG6/EST1A and POT1 CC (PubMed:19179534). Interacts with SHQ1; this interaction may lead to CC the stabilization of DKC1, from the time of its synthesis until its CC association with NOP10, NHP2, and NAF1 at the nascent H/ACA RNA CC (PubMed:19734544, PubMed:19383767). Interacts with HMBOX1 CC (PubMed:23685356). Interacts with DHX36 (PubMed:21846770). CC {ECO:0000269|PubMed:11074001, ECO:0000269|PubMed:15044956, CC ECO:0000269|PubMed:16601202, ECO:0000269|PubMed:16618814, CC ECO:0000269|PubMed:19179534, ECO:0000269|PubMed:19383767, CC ECO:0000269|PubMed:19734544, ECO:0000269|PubMed:20351177, CC ECO:0000269|PubMed:21846770, ECO:0000269|PubMed:23685356, CC ECO:0000269|PubMed:29695869}. CC -!- INTERACTION: CC O60832; Q6NT76: HMBOX1; NbExp=2; IntAct=EBI-713091, EBI-2549423; CC O60832; Q96HR8: NAF1; NbExp=8; IntAct=EBI-713091, EBI-2515597; CC O60832; Q9Y265: RUVBL1; NbExp=9; IntAct=EBI-713091, EBI-353675; CC O60832; Q6PI26: SHQ1; NbExp=2; IntAct=EBI-713091, EBI-2515568; CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus, nucleolus CC {ECO:0000269|PubMed:10556300, ECO:0000269|PubMed:10591218, CC ECO:0000269|PubMed:12429849}. Nucleus, Cajal body CC {ECO:0000250|UniProtKB:P40615}. CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm CC {ECO:0000269|PubMed:21820037}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O60832-1; Sequence=Displayed; CC Name=3; CC IsoId=O60832-2; Sequence=VSP_042422; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. CC {ECO:0000269|PubMed:10903840}. CC -!- DISEASE: Dyskeratosis congenita, X-linked (DKCX) [MIM:305000]: A rare, CC progressive bone marrow failure syndrome characterized by the triad of CC reticulated skin hyperpigmentation, nail dystrophy, and mucosal CC leukoplakia. Early mortality is often associated with bone marrow CC failure, infections, fatal pulmonary complications, or malignancy. CC {ECO:0000269|PubMed:10364516, ECO:0000269|PubMed:15304085, CC ECO:0000269|PubMed:17417794, ECO:0000269|PubMed:18802941, CC ECO:0000269|PubMed:19734544, ECO:0000269|PubMed:19879169, CC ECO:0000269|PubMed:21602826, ECO:0000269|PubMed:25219674, CC ECO:0000269|PubMed:9590285}. Note=The disease is caused by variants CC affecting the gene represented in this entry. Reduced rRNA CC pseudouridine levels in cells from patients (PubMed:25219674). CC {ECO:0000269|PubMed:25219674}. CC -!- DISEASE: Hoyeraal-Hreidarsson syndrome (HHS) [MIM:305000]: A clinically CC severe variant of dyskeratosis congenita that is characterized by CC multisystem involvement, early onset in utero, and often results in CC death in childhood. Affected individuals show intrauterine growth CC retardation, microcephaly, cerebellar hypoplasia, delayed development, CC and bone marrow failure resulting in immunodeficiency. CC {ECO:0000269|PubMed:10583221, ECO:0000269|PubMed:12437656, CC ECO:0000269|PubMed:19734544, ECO:0000269|PubMed:24914498}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Cataracts, hearing impairment, nephrotic syndrome, and CC enterocolitis 1 (CHINE1) [MIM:301108]: An X-linked dominant disorder CC characterized by infantile onset of steroid-resistant nephrotic CC syndrome, cataracts, sensorineural deafness, and enterocolitis. Males CC are more severely affected than females, and death occurs in early CC childhood. Affected females develop early-onset hearing impairment, CC early-onset cataracts, but only rarely have nephrotic syndrome. They do CC not have enterocolitis. {ECO:0000269|PubMed:32554502}. Note=The disease CC may be caused by variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the pseudouridine synthase TruB family. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=DKC1base; Note=DKC1 mutation db; CC URL="http://structure.bmc.lu.se/idbase/DKC1base/"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/157/DKC1"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AJ224481; CAA11970.1; -; Genomic_DNA. DR EMBL; AJ010395; CAB51168.1; -; Genomic_DNA. DR EMBL; AJ010396; CAB51168.1; JOINED; Genomic_DNA. DR EMBL; AF067008; AAD11815.1; -; mRNA. DR EMBL; AF067023; AAD20232.1; -; Genomic_DNA. DR EMBL; AF067009; AAD20232.1; JOINED; Genomic_DNA. DR EMBL; AF067010; AAD20232.1; JOINED; Genomic_DNA. DR EMBL; AF067011; AAD20232.1; JOINED; Genomic_DNA. DR EMBL; AF067012; AAD20232.1; JOINED; Genomic_DNA. DR EMBL; AF067013; AAD20232.1; JOINED; Genomic_DNA. DR EMBL; AF067014; AAD20232.1; JOINED; Genomic_DNA. DR EMBL; AF067015; AAD20232.1; JOINED; Genomic_DNA. DR EMBL; AF067016; AAD20232.1; JOINED; Genomic_DNA. DR EMBL; AF067017; AAD20232.1; JOINED; Genomic_DNA. DR EMBL; AF067018; AAD20232.1; JOINED; Genomic_DNA. DR EMBL; AF067019; AAD20232.1; JOINED; Genomic_DNA. DR EMBL; AF067020; AAD20232.1; JOINED; Genomic_DNA. DR EMBL; AF067021; AAD20232.1; JOINED; Genomic_DNA. DR EMBL; AF067022; AAD20232.1; JOINED; Genomic_DNA. DR EMBL; U59151; AAB94299.1; -; mRNA. DR EMBL; JF279874; ADX66370.1; -; mRNA. DR EMBL; AC109993; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC009928; AAH09928.1; -; mRNA. DR EMBL; BC010015; AAH10015.1; -; mRNA. DR CCDS; CCDS14761.1; -. [O60832-1] DR RefSeq; NP_001135935.1; NM_001142463.2. DR RefSeq; NP_001275676.1; NM_001288747.1. [O60832-2] DR RefSeq; NP_001354.1; NM_001363.4. [O60832-1] DR PDB; 7BGB; EM; 3.39 A; C/G=1-514. DR PDB; 7TRC; EM; 3.30 A; C/G=1-514. DR PDB; 7V9A; EM; 3.94 A; C/G=1-514. DR PDBsum; 7BGB; -. DR PDBsum; 7TRC; -. DR PDBsum; 7V9A; -. DR AlphaFoldDB; O60832; -. DR EMDB; EMD-12177; -. DR EMDB; EMD-26085; -. DR EMDB; EMD-31813; -. DR EMDB; EMD-31814; -. DR SMR; O60832; -. DR BioGRID; 108080; 382. DR ComplexPortal; CPX-265; Telomerase holoenzyme complex. DR CORUM; O60832; -. DR DIP; DIP-40645N; -. DR IntAct; O60832; 128. DR MINT; O60832; -. DR STRING; 9606.ENSP00000358563; -. DR GlyGen; O60832; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O60832; -. DR MetOSite; O60832; -. DR PhosphoSitePlus; O60832; -. DR SwissPalm; O60832; -. DR BioMuta; DKC1; -. DR EPD; O60832; -. DR jPOST; O60832; -. DR MassIVE; O60832; -. DR MaxQB; O60832; -. DR PaxDb; 9606-ENSP00000358563; -. DR PeptideAtlas; O60832; -. DR ProteomicsDB; 49624; -. [O60832-1] DR ProteomicsDB; 49625; -. [O60832-2] DR Pumba; O60832; -. DR Antibodypedia; 418; 471 antibodies from 39 providers. DR DNASU; 1736; -. DR Ensembl; ENST00000369550.10; ENSP00000358563.5; ENSG00000130826.19. [O60832-1] DR GeneID; 1736; -. DR KEGG; hsa:1736; -. DR MANE-Select; ENST00000369550.10; ENSP00000358563.5; NM_001363.5; NP_001354.1. DR UCSC; uc004fmm.5; human. [O60832-1] DR AGR; HGNC:2890; -. DR CTD; 1736; -. DR DisGeNET; 1736; -. DR GeneCards; DKC1; -. DR GeneReviews; DKC1; -. DR HGNC; HGNC:2890; DKC1. DR HPA; ENSG00000130826; Low tissue specificity. DR MalaCards; DKC1; -. DR MIM; 300126; gene. DR MIM; 301108; phenotype. DR MIM; 305000; phenotype. DR neXtProt; NX_O60832; -. DR OpenTargets; ENSG00000130826; -. DR Orphanet; 1775; Dyskeratosis congenita. DR Orphanet; 3322; Hoyeraal-Hreidarsson syndrome. DR PharmGKB; PA27344; -. DR VEuPathDB; HostDB:ENSG00000130826; -. DR eggNOG; KOG2529; Eukaryota. DR GeneTree; ENSGT00510000047092; -. DR HOGENOM; CLU_032087_3_2_1; -. DR InParanoid; O60832; -. DR OMA; CIVRLHD; -. DR OrthoDB; 5472308at2759; -. DR PhylomeDB; O60832; -. DR TreeFam; TF300354; -. DR PathwayCommons; O60832; -. DR Reactome; R-HSA-171319; Telomere Extension By Telomerase. DR Reactome; R-HSA-6790901; rRNA modification in the nucleus and cytosol. DR SignaLink; O60832; -. DR SIGNOR; O60832; -. DR BioGRID-ORCS; 1736; 421 hits in 785 CRISPR screens. DR ChiTaRS; DKC1; human. DR GeneWiki; Dyskerin; -. DR GenomeRNAi; 1736; -. DR Pharos; O60832; Tbio. DR PRO; PR:O60832; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; O60832; Protein. DR Bgee; ENSG00000130826; Expressed in secondary oocyte and 208 other cell types or tissues. DR ExpressionAtlas; O60832; baseline and differential. DR GO; GO:0072589; C:box H/ACA scaRNP complex; TAS:BHF-UCL. DR GO; GO:0031429; C:box H/ACA snoRNP complex; IDA:BHF-UCL. DR GO; GO:0090661; C:box H/ACA telomerase RNP complex; IDA:BHF-UCL. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0001650; C:fibrillar center; IDA:HPA. DR GO; GO:0005730; C:nucleolus; TAS:ProtInc. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:LIFEdb. DR GO; GO:0005697; C:telomerase holoenzyme complex; IDA:UniProtKB. DR GO; GO:0034513; F:box H/ACA snoRNA binding; IPI:BHF-UCL. DR GO; GO:0009982; F:pseudouridine synthase activity; IMP:UniProtKB. DR GO; GO:0003723; F:RNA binding; IPI:BHF-UCL. DR GO; GO:0003720; F:telomerase activity; IDA:UniProtKB. DR GO; GO:0070034; F:telomerase RNA binding; IPI:BHF-UCL. DR GO; GO:0000495; P:box H/ACA RNA 3'-end processing; IBA:GO_Central. DR GO; GO:0000455; P:enzyme-directed rRNA pseudouridine synthesis; IMP:UniProtKB. DR GO; GO:1990481; P:mRNA pseudouridine synthesis; IBA:GO_Central. DR GO; GO:1904851; P:positive regulation of establishment of protein localization to telomere; IMP:BHF-UCL. DR GO; GO:1904871; P:positive regulation of protein localization to Cajal body; HMP:BHF-UCL. DR GO; GO:0051973; P:positive regulation of telomerase activity; IMP:BHF-UCL. DR GO; GO:1904874; P:positive regulation of telomerase RNA localization to Cajal body; IMP:BHF-UCL. DR GO; GO:0032212; P:positive regulation of telomere maintenance via telomerase; IEA:Ensembl. DR GO; GO:1904872; P:regulation of telomerase RNA localization to Cajal body; IMP:BHF-UCL. DR GO; GO:0006396; P:RNA processing; TAS:ProtInc. DR GO; GO:0006364; P:rRNA processing; TAS:ProtInc. DR GO; GO:0031118; P:rRNA pseudouridine synthesis; IBA:GO_Central. DR GO; GO:0090666; P:scaRNA localization to Cajal body; IMP:BHF-UCL. DR GO; GO:0031120; P:snRNA pseudouridine synthesis; IBA:GO_Central. DR GO; GO:0090669; P:telomerase RNA stabilization; IMP:BHF-UCL. DR GO; GO:0007004; P:telomere maintenance via telomerase; IDA:UniProtKB. DR CDD; cd02572; PseudoU_synth_hDyskerin; 1. DR CDD; cd21148; PUA_Cbf5; 1. DR Gene3D; 3.30.2350.10; Pseudouridine synthase; 1. DR Gene3D; 2.30.130.10; PUA domain; 1. DR InterPro; IPR012960; Dyskerin-like. DR InterPro; IPR020103; PsdUridine_synth_cat_dom_sf. DR InterPro; IPR002501; PsdUridine_synth_N. DR InterPro; IPR002478; PUA. DR InterPro; IPR015947; PUA-like_sf. DR InterPro; IPR036974; PUA_sf. DR InterPro; IPR004802; tRNA_PsdUridine_synth_B_fam. DR InterPro; IPR032819; TruB_C. DR InterPro; IPR004521; Uncharacterised_CHP00451. DR NCBIfam; TIGR00425; CBF5; 1. DR NCBIfam; TIGR00451; unchar_dom_2; 1. DR PANTHER; PTHR23127; CENTROMERE/MICROTUBULE BINDING PROTEIN CBF5; 1. DR PANTHER; PTHR23127:SF0; H_ACA RIBONUCLEOPROTEIN COMPLEX SUBUNIT DKC1; 1. DR Pfam; PF08068; DKCLD; 1. DR Pfam; PF01472; PUA; 1. DR Pfam; PF16198; TruB_C_2; 1. DR Pfam; PF01509; TruB_N; 1. DR SMART; SM01136; DKCLD; 1. DR SMART; SM00359; PUA; 1. DR SUPFAM; SSF55120; Pseudouridine synthase; 1. DR SUPFAM; SSF88697; PUA domain-like; 1. DR PROSITE; PS50890; PUA; 1. DR SWISS-2DPAGE; O60832; -. DR Genevisible; O60832; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cataract; Cytoplasm; KW Deafness; Direct protein sequencing; Disease variant; KW Dyskeratosis congenita; Isomerase; Isopeptide bond; Nucleus; KW Phosphoprotein; Reference proteome; Ribonucleoprotein; Ribosome biogenesis; KW RNA-binding; rRNA processing; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|Ref.8, ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22223895" FT CHAIN 2..514 FT /note="H/ACA ribonucleoprotein complex subunit DKC1" FT /id="PRO_0000121983" FT DOMAIN 296..371 FT /note="PUA" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00161" FT REGION 2..21 FT /note="Nucleolar localization" FT REGION 443..514 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 446..514 FT /note="Nuclear and nucleolar localization" FT ACT_SITE 125 FT /note="Nucleophile" FT /evidence="ECO:0000250|UniProtKB:P60340" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000269|Ref.8, ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22223895" FT MOD_RES 21 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692" FT MOD_RES 387 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 451 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 453 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 455 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 458 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q9ESX5" FT MOD_RES 485 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 494 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:16964243, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 513 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT CROSSLNK 20 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 39 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 43 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 191 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 394 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 413 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT /evidence="ECO:0007744|PubMed:25114211" FT CROSSLNK 413 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:25218447, FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:25772364, FT ECO:0007744|PubMed:28112733" FT CROSSLNK 424 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 433 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 467 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 420..514 FT /note="SESAKKEVVAEVVKAPQVVAEAAKTAKRKRESESESDETPPAAPQLIKKEKK FT KSKKDKKAKAGLESGAEPGDGDSDTTKKKKKKKKAKEVELVSE -> R (in FT isoform 3)" FT /evidence="ECO:0000303|PubMed:21820037" FT /id="VSP_042422" FT VARIANT 2 FT /note="A -> V (in DKCX; dbSNP:rs121912303)" FT /evidence="ECO:0000269|PubMed:10364516" FT /id="VAR_010076" FT VARIANT 36 FT /note="F -> V (in DKCX; dbSNP:rs121912293)" FT /evidence="ECO:0000269|PubMed:9590285" FT /id="VAR_006811" FT VARIANT 37 FT /note="Missing (in DKCX; results in mislocalization of the FT telomerase complex without affecting telomerase activity; FT dbSNP:rs137854489)" FT /evidence="ECO:0000269|PubMed:21602826, FT ECO:0000269|PubMed:9590285" FT /id="VAR_006812" FT VARIANT 38 FT /note="I -> T (in HHS; dbSNP:rs28936072)" FT /evidence="ECO:0000269|PubMed:12437656" FT /id="VAR_015674" FT VARIANT 39 FT /note="K -> E (in DKCX; dbSNP:rs121912296)" FT /evidence="ECO:0000269|PubMed:10364516" FT /id="VAR_010077" FT VARIANT 40 FT /note="P -> R (in DKCX; dbSNP:rs121912292)" FT /evidence="ECO:0000269|PubMed:9590285" FT /id="VAR_006813" FT VARIANT 41 FT /note="E -> K (in DKCX; dbSNP:rs121912302)" FT /evidence="ECO:0000269|PubMed:10364516" FT /id="VAR_010078" FT VARIANT 49 FT /note="T -> M (in HHS; increases interaction with SHQ1; FT dbSNP:rs121912304)" FT /evidence="ECO:0000269|PubMed:10583221, FT ECO:0000269|PubMed:19734544, ECO:0000269|PubMed:24914498" FT /id="VAR_015675" FT VARIANT 54 FT /note="L -> V (in DKCX; results in mislocalization of the FT telomerase complex without affecting telomerase activity)" FT /evidence="ECO:0000269|PubMed:21602826" FT /id="VAR_080707" FT VARIANT 56 FT /note="L -> S (in DKCX; due to a 2 nucleotide inversion; FT dbSNP:rs121912287)" FT /evidence="ECO:0000269|PubMed:18802941" FT /id="VAR_063821" FT VARIANT 65 FT /note="R -> T (in DKCX; dbSNP:rs121912301)" FT /evidence="ECO:0000269|PubMed:10364516" FT /id="VAR_010079" FT VARIANT 66 FT /note="T -> A (in DKCX; decreases interaction with SHQ1; FT dbSNP:rs121912297)" FT /evidence="ECO:0000269|PubMed:10364516, FT ECO:0000269|PubMed:19734544" FT /id="VAR_010080" FT VARIANT 72 FT /note="L -> F (in DKCX; dbSNP:rs121912306)" FT /evidence="ECO:0000269|PubMed:17417794" FT /id="VAR_063822" FT VARIANT 72 FT /note="L -> Y (in DKCX; requires 2 nucleotide FT substitutions; dbSNP:rs121912294)" FT /evidence="ECO:0000269|PubMed:9590285" FT /id="VAR_006814" FT VARIANT 121 FT /note="S -> G (in HHS; no effect on interaction with SHQ1; FT dbSNP:rs121912305)" FT /evidence="ECO:0000269|PubMed:10583221, FT ECO:0000269|PubMed:19734544" FT /id="VAR_015676" FT VARIANT 206 FT /note="E -> K (in CHINE1; likely pathogenic; decreased rRNA FT pseudouridine synthesis in peripheral blood cells from a FT severely affected female; unable to fully rescue FT developmental defects in dkc1-null zebrafish morphants; FT does not affect interaction with NOP10)" FT /evidence="ECO:0000269|PubMed:32554502" FT /id="VAR_088623" FT VARIANT 223 FT /note="G -> D (in dbSNP:rs2728533)" FT /id="VAR_022553" FT VARIANT 317 FT /note="L -> F (in DKCX; dbSNP:rs121912290)" FT /evidence="ECO:0000269|PubMed:19879169" FT /id="VAR_063823" FT VARIANT 321 FT /note="L -> V (in DKCX; dbSNP:rs2728726)" FT /evidence="ECO:0000269|PubMed:10364516" FT /id="VAR_010081" FT VARIANT 322 FT /note="R -> Q (in DKCX; dbSNP:rs121912291)" FT /evidence="ECO:0000269|PubMed:19879169" FT /id="VAR_063824" FT VARIANT 350 FT /note="M -> I (in DKCX; increases interaction with SHQ1; FT dbSNP:rs121912298)" FT /evidence="ECO:0000269|PubMed:10364516, FT ECO:0000269|PubMed:19734544" FT /id="VAR_010082" FT VARIANT 350 FT /note="M -> T (in DKCX; decreases interaction with SHQ1; FT dbSNP:rs121912300)" FT /evidence="ECO:0000269|PubMed:10364516, FT ECO:0000269|PubMed:19734544" FT /id="VAR_010083" FT VARIANT 353 FT /note="A -> V (in DKCX and HHS; increases interaction with FT SHQ1; dbSNP:rs121912288)" FT /evidence="ECO:0000269|PubMed:10364516, FT ECO:0000269|PubMed:15304085, ECO:0000269|PubMed:19734544" FT /id="VAR_009264" FT VARIANT 402 FT /note="G -> E (in DKCX; dbSNP:rs121912295)" FT /evidence="ECO:0000269|PubMed:9590285" FT /id="VAR_006815" FT VARIANT 402 FT /note="G -> R (in DKCX; dbSNP:rs121912299)" FT /evidence="ECO:0000269|PubMed:10364516" FT /id="VAR_010084" FT VARIANT 409 FT /note="P -> L (in DKCX; dbSNP:rs121912289)" FT /evidence="ECO:0000269|PubMed:15304085" FT /id="VAR_063825" FT MUTAGEN 353 FT /note="A->R: Increases interaction with SHQ1." FT /evidence="ECO:0000269|PubMed:19734544" FT CONFLICT 37 FT /note="L -> F (in Ref. 4; AAB94299)" FT /evidence="ECO:0000305" FT CONFLICT 285 FT /note="V -> F (in Ref. 7; AAH09928)" FT /evidence="ECO:0000305" FT CONFLICT 446 FT /note="K -> KVSGMLSSVWN (in Ref. 2; CAB51168)" FT /evidence="ECO:0000305" FT HELIX 49..51 FT /evidence="ECO:0007829|PDB:7TRC" FT TURN 57..60 FT /evidence="ECO:0007829|PDB:7TRC" FT STRAND 61..64 FT /evidence="ECO:0007829|PDB:7TRC" FT HELIX 83..88 FT /evidence="ECO:0007829|PDB:7TRC" FT STRAND 89..96 FT /evidence="ECO:0007829|PDB:7TRC" FT STRAND 98..100 FT /evidence="ECO:0007829|PDB:7TRC" FT HELIX 102..113 FT /evidence="ECO:0007829|PDB:7TRC" FT STRAND 118..122 FT /evidence="ECO:0007829|PDB:7TRC" FT STRAND 129..136 FT /evidence="ECO:0007829|PDB:7TRC" FT HELIX 137..143 FT /evidence="ECO:0007829|PDB:7TRC" FT HELIX 144..147 FT /evidence="ECO:0007829|PDB:7TRC" FT STRAND 152..158 FT /evidence="ECO:0007829|PDB:7TRC" FT HELIX 166..174 FT /evidence="ECO:0007829|PDB:7TRC" FT STRAND 178..182 FT /evidence="ECO:0007829|PDB:7TRC" FT STRAND 195..208 FT /evidence="ECO:0007829|PDB:7TRC" FT TURN 209..212 FT /evidence="ECO:0007829|PDB:7TRC" FT STRAND 213..220 FT /evidence="ECO:0007829|PDB:7TRC" FT HELIX 226..237 FT /evidence="ECO:0007829|PDB:7TRC" FT STRAND 242..248 FT /evidence="ECO:0007829|PDB:7TRC" FT STRAND 254..259 FT /evidence="ECO:0007829|PDB:7TRC" FT HELIX 263..276 FT /evidence="ECO:0007829|PDB:7TRC" FT HELIX 282..284 FT /evidence="ECO:0007829|PDB:7TRC" FT HELIX 289..292 FT /evidence="ECO:0007829|PDB:7TRC" FT STRAND 299..301 FT /evidence="ECO:0007829|PDB:7TRC" FT HELIX 303..311 FT /evidence="ECO:0007829|PDB:7TRC" FT TURN 317..319 FT /evidence="ECO:0007829|PDB:7TRC" FT STRAND 320..323 FT /evidence="ECO:0007829|PDB:7TRC" FT STRAND 332..336 FT /evidence="ECO:0007829|PDB:7TRC" FT STRAND 338..340 FT /evidence="ECO:0007829|PDB:7BGB" FT STRAND 342..348 FT /evidence="ECO:0007829|PDB:7TRC" FT TURN 352..357 FT /evidence="ECO:0007829|PDB:7TRC" FT STRAND 360..369 FT /evidence="ECO:0007829|PDB:7TRC" FT STRAND 373..376 FT /evidence="ECO:0007829|PDB:7TRC" FT STRAND 383..387 FT /evidence="ECO:0007829|PDB:7TRC" FT HELIX 388..391 FT /evidence="ECO:0007829|PDB:7TRC" SQ SEQUENCE 514 AA; 57674 MW; 12474DBEEFEB471C CRC64; MADAEVIILP KKHKKKKERK SLPEEDVAEI QHAEEFLIKP ESKVAKLDTS QWPLLLKNFD KLNVRTTHYT PLACGSNPLK REIGDYIRTG FINLDKPSNP SSHEVVAWIR RILRVEKTGH SGTLDPKVTG CLIVCIERAT RLVKSQQSAG KEYVGIVRLH NAIEGGTQLS RALETLTGAL FQRPPLIAAV KRQLRVRTIY ESKMIEYDPE RRLGIFWVSC EAGTYIRTLC VHLGLLLGVG GQMQELRRVR SGVMSEKDHM VTMHDVLDAQ WLYDNHKDES YLRRVVYPLE KLLTSHKRLV MKDSAVNAIC YGAKIMLPGV LRYEDGIEVN QEIVVITTKG EAICMAIALM TTAVISTCDH GIVAKIKRVI MERDTYPRKW GLGPKASQKK LMIKQGLLDK HGKPTDSTPA TWKQEYVDYS ESAKKEVVAE VVKAPQVVAE AAKTAKRKRE SESESDETPP AAPQLIKKEK KKSKKDKKAK AGLESGAEPG DGDSDTTKKK KKKKKAKEVE LVSE //