DKC1_HUMAN
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 03-AUG-2022, entry version 227.
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).
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). This involves the
CC isomerization of uridine such that the ribose is subsequently attached
CC to C5, instead of the normal N1 (PubMed:25219674). Each rRNA can
CC contain up to 100 pseudouridine ('psi') residues, which may serve to
CC stabilize the conformation of rRNAs. Required for ribosome biogenesis
CC and telomere maintenance (PubMed:19179534, PubMed:25219674). Also
CC required for correct processing or intranuclear trafficking of TERC,
CC the RNA component of the telomerase reverse transcriptase (TERT)
CC holoenzyme (PubMed:19179534). {ECO:0000269|PubMed:19179534,
CC ECO:0000269|PubMed:25219674}.
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}. Note=Also localized to Cajal bodies
CC (coiled bodies). {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 -!- 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="http://atlasgeneticsoncology.org/Genes/DKC1ID157.html";
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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 CCDS; CCDS76062.1; -. [O60832-2]
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; 7V9A; EM; 3.94 A; C/G=1-514.
DR PDBsum; 7BGB; -.
DR PDBsum; 7V9A; -.
DR AlphaFoldDB; O60832; -.
DR SMR; O60832; -.
DR BioGRID; 108080; 326.
DR ComplexPortal; CPX-265; Telomerase holoenzyme complex.
DR CORUM; O60832; -.
DR DIP; DIP-40645N; -.
DR IntAct; O60832; 122.
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 SWISS-2DPAGE; O60832; -.
DR EPD; O60832; -.
DR jPOST; O60832; -.
DR MassIVE; O60832; -.
DR MaxQB; O60832; -.
DR PaxDb; O60832; -.
DR PeptideAtlas; O60832; -.
DR PRIDE; O60832; -.
DR ProteomicsDB; 49624; -. [O60832-1]
DR ProteomicsDB; 49625; -. [O60832-2]
DR Antibodypedia; 418; 425 antibodies from 39 providers.
DR DNASU; 1736; -.
DR Ensembl; ENST00000369550.10; ENSP00000358563.5; ENSG00000130826.18. [O60832-1]
DR Ensembl; ENST00000620277.4; ENSP00000478387.1; ENSG00000130826.18. [O60832-2]
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 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; 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; GPFKEDE; -.
DR OrthoDB; 1070373at2759; -.
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; 389 hits in 709 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 206 other tissues.
DR ExpressionAtlas; O60832; baseline and differential.
DR Genevisible; O60832; HS.
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 Gene3D; 2.30.130.10; -; 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 PANTHER; PTHR23127; PTHR23127; 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; SSF55120; 1.
DR SUPFAM; SSF88697; SSF88697; 1.
DR TIGRFAMs; TIGR00425; CBF5; 1.
DR TIGRFAMs; TIGR00451; unchar_dom_2; 1.
DR PROSITE; PS50890; PUA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm;
KW Direct protein sequencing; Disease variant; Dyskeratosis congenita;
KW Isomerase; Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome;
KW Ribonucleoprotein; Ribosome biogenesis; RNA-binding; rRNA processing;
KW 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 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 TURN 57..60
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 61..65
FT /evidence="ECO:0007829|PDB:7BGB"
FT TURN 83..88
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 89..96
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 98..100
FT /evidence="ECO:0007829|PDB:7BGB"
FT HELIX 105..112
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 118..122
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 129..137
FT /evidence="ECO:0007829|PDB:7BGB"
FT HELIX 138..142
FT /evidence="ECO:0007829|PDB:7BGB"
FT TURN 144..146
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 147..152
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 155..158
FT /evidence="ECO:0007829|PDB:7BGB"
FT HELIX 167..174
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 178..182
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 195..197
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 204..208
FT /evidence="ECO:0007829|PDB:7BGB"
FT TURN 209..212
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 213..216
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 219..221
FT /evidence="ECO:0007829|PDB:7BGB"
FT HELIX 226..235
FT /evidence="ECO:0007829|PDB:7BGB"
FT TURN 236..238
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 243..247
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 254..259
FT /evidence="ECO:0007829|PDB:7BGB"
FT TURN 263..267
FT /evidence="ECO:0007829|PDB:7BGB"
FT HELIX 268..276
FT /evidence="ECO:0007829|PDB:7BGB"
FT TURN 280..285
FT /evidence="ECO:0007829|PDB:7BGB"
FT HELIX 289..291
FT /evidence="ECO:0007829|PDB:7BGB"
FT TURN 292..295
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 296..301
FT /evidence="ECO:0007829|PDB:7BGB"
FT HELIX 306..311
FT /evidence="ECO:0007829|PDB:7BGB"
FT TURN 317..319
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 320..323
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 332..336
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 338..340
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 342..348
FT /evidence="ECO:0007829|PDB:7BGB"
FT HELIX 354..356
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 360..362
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 364..369
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 373..376
FT /evidence="ECO:0007829|PDB:7BGB"
FT TURN 388..391
FT /evidence="ECO:0007829|PDB:7BGB"
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
