TCAB1_HUMAN
ID TCAB1_HUMAN Reviewed; 548 AA.
AC Q9BUR4; B3KPR9; D3DTQ4; Q08ET9; Q9NW09;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Telomerase Cajal body protein 1 {ECO:0000303|PubMed:19179534};
DE AltName: Full=WD repeat-containing protein 79 {ECO:0000303|PubMed:19285445};
DE AltName: Full=WD40 repeat-containing protein antisense to TP53 gene {ECO:0000303|PubMed:19250907};
DE Short=WRAP53beta {ECO:0000303|PubMed:25512560};
GN Name=WRAP53 {ECO:0000303|PubMed:19250907, ECO:0000312|HGNC:HGNC:25522};
GN Synonyms=TCAB1 {ECO:0000303|PubMed:19179534},
GN WDR79 {ECO:0000303|PubMed:19285445};
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].
RA Hammarsund M.;
RT "Endogenous p53 antisense transcript Wrap53 is required for p53
RT stabilization upon DNA damage.";
RL Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLY-68.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-54, AND IDENTIFICATION BY
RP 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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-90, 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 [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-54, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-26; SER-30; SER-54; SER-85;
RP SER-90; SER-112; SER-114; THR-489 AND SER-491, AND IDENTIFICATION BY MASS
RP 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 [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [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 [11]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND ALTERNATIVE
RP SPLICING.
RX PubMed=19250907; DOI=10.1016/j.molcel.2009.01.028;
RA Mahmoudi S., Henriksson S., Corcoran M., Mendez-Vidal C., Wiman K.G.,
RA Farnebo M.;
RT "Wrap53, a natural p53 antisense transcript required for p53 induction upon
RT DNA damage.";
RL Mol. Cell 33:462-471(2009).
RN [12]
RP FUNCTION, RNA-BINDING, AND SUBCELLULAR LOCATION.
RX PubMed=19285445; DOI=10.1016/j.molcel.2009.02.020;
RA Tycowski K.T., Shu M.D., Kukoyi A., Steitz J.A.;
RT "A conserved WD40 protein binds the Cajal body localization signal of
RT scaRNP particles.";
RL Mol. Cell 34:47-57(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-85; SER-90; SER-112; SER-114;
RP THR-489 AND SER-491, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [14]
RP FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY,
RP IDENTIFICATION IN THE TELOMERASE HOLOENZYME COMPLEX, AND RNA-BINDING.
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 [15]
RP IDENTIFICATION IN THE TELOMERASE HOLOENZYME COMPLEX, RNA-BINDING, AND
RP FUNCTION.
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 [16]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH SMN1 AND COIL.
RX PubMed=21072240; DOI=10.1371/journal.pbio.1000521;
RA Mahmoudi S., Henriksson S., Weibrecht I., Smith S., Soederberg O.,
RA Stroemblad S., Wiman K.G., Farnebo M.;
RT "WRAP53 is essential for Cajal body formation and for targeting the
RT survival of motor neuron complex to Cajal bodies.";
RL PLoS Biol. 8:E1000521-E1000521(2010).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-26; SER-30; SER-90 AND
RP SER-491, AND IDENTIFICATION BY MASS SPECTROMETRY [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 [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-491, AND IDENTIFICATION BY
RP MASS 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 [19]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22547674; DOI=10.1128/mcb.00379-12;
RA Stern J.L., Zyner K.G., Pickett H.A., Cohen S.B., Bryan T.M.;
RT "Telomerase recruitment requires both TCAB1 and Cajal bodies
RT independently.";
RL Mol. Cell. Biol. 32:2384-2395(2012).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-54; SER-64; SER-90 AND
RP SER-491, AND IDENTIFICATION BY MASS SPECTROMETRY [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 [21]
RP INTERACTION WITH THE TRIC COMPLEX.
RX PubMed=25467444; DOI=10.1016/j.cell.2014.10.059;
RA Freund A., Zhong F.L., Venteicher A.S., Meng Z., Veenstra T.D., Frydman J.,
RA Artandi S.E.;
RT "Proteostatic control of telomerase function through TRiC-mediated folding
RT of TCAB1.";
RL Cell 159:1389-1403(2014).
RN [22]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH RNF8.
RX PubMed=25512560; DOI=10.1101/gad.246546.114;
RA Henriksson S., Rassoolzadeh H., Hedstroem E., Coucoravas C., Julner A.,
RA Goldstein M., Imreh G., Zhivotovsky B., Kastan M.B., Helleday T.,
RA Farnebo M.;
RT "The scaffold protein WRAP53beta orchestrates the ubiquitin response
RT critical for DNA double-strand break repair.";
RL Genes Dev. 28:2726-2738(2014).
RN [23]
RP SUBCELLULAR LOCATION.
RX PubMed=24318571; DOI=10.1007/s00418-013-1166-x;
RA Lee J.H., Lee Y.S., Jeong S.A., Khadka P., Roth J., Chung I.K.;
RT "Catalytically active telomerase holoenzyme is assembled in the dense
RT fibrillar component of the nucleolus during S phase.";
RL Histochem. Cell Biol. 141:137-152(2014).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-54; SER-85 AND SER-90, AND
RP IDENTIFICATION BY 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 [25]
RP FUNCTION, IDENTIFICATION IN THE TELOMERASE HOLOENZYME COMPLEX, RNA-BINDING,
RP AND SUBCELLULAR LOCATION.
RX PubMed=26170453; DOI=10.1074/jbc.m115.659359;
RA Vogan J.M., Collins K.;
RT "Dynamics of Human Telomerase Holoenzyme Assembly and Subunit Exchange
RT across the Cell Cycle.";
RL J. Biol. Chem. 290:21320-21335(2015).
RN [26]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH H2AX.
RX PubMed=26734725; DOI=10.1080/19491034.2015.1106675;
RA Rassoolzadeh H., Coucoravas C., Farnebo M.;
RT "The proximity ligation assay reveals that at DNA double-strand breaks
RT WRAP53beta associates with gammaH2AX and controls interactions between RNF8
RT and MDC1.";
RL Nucleus 6:417-424(2015).
RN [27]
RP FUNCTION.
RX PubMed=27525486; DOI=10.7554/elife.18221;
RA Vogan J.M., Zhang X., Youmans D.T., Regalado S.G., Johnson J.Z.,
RA Hockemeyer D., Collins K.;
RT "Minimized human telomerase maintains telomeres and resolves endogenous
RT roles of H/ACA proteins, TCAB1, and Cajal bodies.";
RL Elife 5:0-0(2016).
RN [28]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH H2AX, PHOSPHORYLATION AT
RP SER-64, AND MUTAGENESIS OF SER-64.
RX PubMed=27715493; DOI=10.1080/15476286.2016.1243647;
RA Coucoravas C., Dhanjal S., Henriksson S., Boehm S., Farnebo M.;
RT "Phosphorylation of the Cajal body protein WRAP53beta by ATM promotes its
RT involvement in the DNA damage response.";
RL RNA Biol. 14:804-813(2017).
RN [29]
RP INDUCTION (MICROBIAL INFECTION).
RX PubMed=28607398; DOI=10.1038/s41598-017-03156-3;
RA Wang K., Ge Y., Ni C., Cui B., Du J., Zhang B., Hu X., Chen J., Xiao L.,
RA Sun C., Li Y.;
RT "Epstein-Barr virus-induced up-regulation of TCAB1 is involved in the DNA
RT damage response in nasopharyngeal carcinoma.";
RL Sci. Rep. 7:3218-3218(2017).
RN [30]
RP FUNCTION, SUBCELLULAR LOCATION, AND RNA-BINDING.
RX PubMed=29804836; DOI=10.1016/j.cell.2018.04.039;
RA Chen L., Roake C.M., Freund A., Batista P.J., Tian S., Yin Y.A.,
RA Gajera C.R., Lin S., Lee B., Pech M.F., Venteicher A.S., Das R.,
RA Chang H.Y., Artandi S.E.;
RT "An Activity Switch in Human Telomerase Based on RNA Conformation and
RT Shaped by TCAB1.";
RL Cell 0:0-0(2018).
RN [31]
RP STRUCTURE BY ELECTRON MICROSCOPY (7.7 ANGSTROMS) OF THE TELOMERASE
RP HOLOENZYME COMPLEX, IDENTIFICATION IN THE TELOMERASE HOLOENZYME COMPLEX,
RP RNA-BINDING, AND FUNCTION.
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 [32]
RP VARIANTS DKCB3 LEU-164; TYR-376; TRP-398 AND ARG-435, VARIANTS GLY-68 AND
RP GLY-522, AND CHARACTERIZATION OF VARIANTS DKCB3 LEU-164; TYR-376; TRP-398
RP AND ARG-435.
RX PubMed=21205863; DOI=10.1101/gad.2006411;
RA Zhong F., Savage S.A., Shkreli M., Giri N., Jessop L., Myers T., Chen R.,
RA Alter B.P., Artandi S.E.;
RT "Disruption of telomerase trafficking by TCAB1 mutation causes dyskeratosis
RT congenita.";
RL Genes Dev. 25:11-16(2011).
RN [33]
RP VARIANTS DKCB3 TYR-376 AND ARG-435, AND CHARACTERIZATION OF VARIANTS DKCB3
RP TYR-376 AND ARG-435.
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).
CC -!- FUNCTION: RNA chaperone that plays a key role in telomere maintenance
CC and RNA localization to Cajal bodies (PubMed:29804836,
CC PubMed:29695869). Specifically recognizes and binds the Cajal body box
CC (CAB box) present in both small Cajal body RNAs (scaRNAs) and
CC telomerase RNA template component (TERC) (PubMed:19285445,
CC PubMed:20351177, PubMed:29804836, PubMed:29695869). Essential component
CC of the telomerase holoenzyme complex, a ribonucleoprotein complex
CC essential for the replication of chromosome termini that elongates
CC telomeres in most eukaryotes (PubMed:19179534, PubMed:20351177,
CC PubMed:26170453, PubMed:29695869). In the telomerase holoenzyme
CC complex, required to stimulate the catalytic activity of the complex
CC (PubMed:27525486, PubMed:29804836). Acts by specifically binding the
CC CAB box of the TERC RNA and controlling the folding of the CR4/CR5
CC region of the TERC RNA, a critical step for telomerase activity
CC (PubMed:29804836). In addition, also controls telomerase holoenzyme
CC complex localization to Cajal body (PubMed:22547674). During S phase,
CC required for delivery of TERC to telomeres during S phase and for
CC telomerase activity (PubMed:29804836). In addition to its role in
CC telomere maintenance, also required for Cajal body formation, probably
CC by mediating localization of scaRNAs to Cajal bodies (PubMed:19285445,
CC PubMed:21072240). Also plays a role in DNA repair: phosphorylated by
CC ATM in response to DNA damage and relocalizes to sites of DNA double-
CC strand breaks to promote the repair of DNA double-strand breaks
CC (PubMed:25512560, PubMed:27715493). Acts by recruiting the ubiquitin
CC ligase RNF8 to DNA breaks and promote both homologous recombination
CC (HR) and non-homologous end joining (NHEJ) (PubMed:25512560,
CC PubMed:27715493). {ECO:0000269|PubMed:19179534,
CC ECO:0000269|PubMed:19285445, ECO:0000269|PubMed:20351177,
CC ECO:0000269|PubMed:21072240, ECO:0000269|PubMed:22547674,
CC ECO:0000269|PubMed:25512560, ECO:0000269|PubMed:26170453,
CC ECO:0000269|PubMed:27525486, ECO:0000269|PubMed:27715493,
CC ECO:0000269|PubMed:29695869, ECO:0000269|PubMed:29804836}.
CC -!- SUBUNIT: Component of the telomerase holoenzyme complex composed of one
CC molecule 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:19179534,
CC PubMed:20351177, PubMed:26170453, PubMed:29695869). The telomerase
CC holoenzyme complex is associated with TEP1, SMG6/EST1A and POT1
CC (PubMed:19179534). Interacts with the chaperonin-containing T-complex
CC (TRiC) complex; which mediates the folding of WRAP53/TCAB1
CC (PubMed:25467444). Interacts with COIL (PubMed:21072240). Interacts
CC with SMN1 (PubMed:21072240). Interacts with RNF8 (PubMed:25512560).
CC Interacts with histone H2AX (PubMed:26734725, PubMed:27715493).
CC {ECO:0000269|PubMed:19179534, ECO:0000269|PubMed:20351177,
CC ECO:0000269|PubMed:21072240, ECO:0000269|PubMed:25467444,
CC ECO:0000269|PubMed:25512560, ECO:0000269|PubMed:26170453,
CC ECO:0000269|PubMed:26734725, ECO:0000269|PubMed:27715493,
CC ECO:0000269|PubMed:29695869}.
CC -!- INTERACTION:
CC Q9BUR4; P38432: COIL; NbExp=4; IntAct=EBI-2563542, EBI-945751;
CC Q9BUR4; Q16637: SMN2; NbExp=5; IntAct=EBI-2563542, EBI-395421;
CC Q9BUR4; Q5T6F2: UBAP2; NbExp=3; IntAct=EBI-2563542, EBI-2514383;
CC Q9BUR4; Q08AM6: VAC14; NbExp=3; IntAct=EBI-2563542, EBI-2107455;
CC Q9BUR4; Q9BUR4: WRAP53; NbExp=3; IntAct=EBI-2563542, EBI-2563542;
CC Q9BUR4; O77622: CCT6; Xeno; NbExp=2; IntAct=EBI-2563542, EBI-10714431;
CC -!- SUBCELLULAR LOCATION: Nucleus, Cajal body {ECO:0000269|PubMed:19179534,
CC ECO:0000269|PubMed:19285445, ECO:0000269|PubMed:21072240,
CC ECO:0000269|PubMed:22547674, ECO:0000269|PubMed:24318571,
CC ECO:0000269|PubMed:26170453}. Chromosome, telomere
CC {ECO:0000269|PubMed:22547674, ECO:0000269|PubMed:29804836}. Chromosome
CC {ECO:0000269|PubMed:25512560, ECO:0000269|PubMed:26734725,
CC ECO:0000269|PubMed:27715493}. Note=Released from telomerase RNA
CC template component (TERC) in mitotic cells coincident with
CC delocalization from Cajal bodies (PubMed:26170453). In response to DNA
CC damage, localizes to sites of DNA double-strand breaks following
CC phosphorylation by ATM (PubMed:26734725, PubMed:27715493).
CC {ECO:0000269|PubMed:26170453, ECO:0000269|PubMed:26734725,
CC ECO:0000269|PubMed:27715493}.
CC -!- TISSUE SPECIFICITY: Expressed in all tissues and cell lines examined.
CC {ECO:0000269|PubMed:19250907}.
CC -!- INDUCTION: (Microbial infection) Over-expressed following infection by
CC Epstein-Barr virus. {ECO:0000269|PubMed:28607398}.
CC -!- PTM: Phosphorylated at Ser-64 by ATM in response to DNA damage,
CC promoting its interaction with histone H2AX and localization to sites
CC of DNA double-strand breaks. {ECO:0000269|PubMed:27715493}.
CC -!- DISEASE: Dyskeratosis congenita, autosomal recessive, 3 (DKCB3)
CC [MIM:613988]: A rare multisystem disorder caused by defective telomere
CC maintenance. It is characterized by progressive bone marrow failure,
CC and the clinical triad of reticulated skin hyperpigmentation, nail
CC dystrophy, and mucosal leukoplakia. Common but variable features
CC include premature graying, aplastic anemia, low platelets,
CC osteoporosis, pulmonary fibrosis, and liver fibrosis among others.
CC Early mortality is often associated with bone marrow failure,
CC infections, fatal pulmonary complications, or malignancy.
CC {ECO:0000269|PubMed:21205863, ECO:0000269|PubMed:21602826}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: The mRNA encoding this protein plays a critical role in
CC the regulation of p53/TP53 expression at the post-transcriptional
CC level; it is involved both in maintaining basal p53/TP53 mRNA levels
CC and in p53/TP53 induction upon DNA damage.
CC {ECO:0000269|PubMed:19250907}.
CC -!- SIMILARITY: Belongs to the TCAB1 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/WRAP53ID50705ch17p13.html";
CC ---------------------------------------------------------------------------
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DR EMBL; AY766322; AAW92115.1; -; mRNA.
DR EMBL; DQ431240; ABD92817.1; -; mRNA.
DR EMBL; DQ431241; ABD92818.1; -; mRNA.
DR EMBL; AK001247; BAA91579.1; -; mRNA.
DR EMBL; AK056669; BAG51781.1; -; mRNA.
DR EMBL; CH471108; EAW90136.1; -; Genomic_DNA.
DR EMBL; CH471108; EAW90138.1; -; Genomic_DNA.
DR EMBL; CH471108; EAW90139.1; -; Genomic_DNA.
DR EMBL; BC002336; AAH02336.1; -; mRNA.
DR CCDS; CCDS11119.1; -.
DR RefSeq; NP_001137462.1; NM_001143990.1.
DR RefSeq; NP_001137463.1; NM_001143991.1.
DR RefSeq; NP_001137464.1; NM_001143992.1.
DR RefSeq; NP_060551.2; NM_018081.2.
DR PDB; 7BGB; EM; 3.39 A; K=1-548.
DR PDB; 7V9A; EM; 3.94 A; B=1-548.
DR PDBsum; 7BGB; -.
DR PDBsum; 7V9A; -.
DR AlphaFoldDB; Q9BUR4; -.
DR SMR; Q9BUR4; -.
DR BioGRID; 120440; 112.
DR CORUM; Q9BUR4; -.
DR DIP; DIP-56796N; -.
DR IntAct; Q9BUR4; 39.
DR STRING; 9606.ENSP00000324203; -.
DR GlyGen; Q9BUR4; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9BUR4; -.
DR MetOSite; Q9BUR4; -.
DR PhosphoSitePlus; Q9BUR4; -.
DR BioMuta; WRAP53; -.
DR DMDM; 74761275; -.
DR EPD; Q9BUR4; -.
DR jPOST; Q9BUR4; -.
DR MassIVE; Q9BUR4; -.
DR MaxQB; Q9BUR4; -.
DR PaxDb; Q9BUR4; -.
DR PeptideAtlas; Q9BUR4; -.
DR PRIDE; Q9BUR4; -.
DR ProteomicsDB; 79122; -.
DR Antibodypedia; 24336; 80 antibodies from 23 providers.
DR DNASU; 55135; -.
DR Ensembl; ENST00000316024.9; ENSP00000324203.5; ENSG00000141499.17.
DR Ensembl; ENST00000396463.7; ENSP00000379727.3; ENSG00000141499.17.
DR Ensembl; ENST00000431639.6; ENSP00000397219.2; ENSG00000141499.17.
DR Ensembl; ENST00000457584.6; ENSP00000411061.2; ENSG00000141499.17.
DR GeneID; 55135; -.
DR KEGG; hsa:55135; -.
DR MANE-Select; ENST00000396463.7; ENSP00000379727.3; NM_001143992.2; NP_001137464.1.
DR UCSC; uc002gip.4; human.
DR CTD; 55135; -.
DR DisGeNET; 55135; -.
DR GeneCards; WRAP53; -.
DR GeneReviews; WRAP53; -.
DR HGNC; HGNC:25522; WRAP53.
DR HPA; ENSG00000141499; Low tissue specificity.
DR MalaCards; WRAP53; -.
DR MIM; 612661; gene.
DR MIM; 613988; phenotype.
DR neXtProt; NX_Q9BUR4; -.
DR OpenTargets; ENSG00000141499; -.
DR Orphanet; 1775; Dyskeratosis congenita.
DR PharmGKB; PA164727568; -.
DR VEuPathDB; HostDB:ENSG00000141499; -.
DR eggNOG; KOG2919; Eukaryota.
DR GeneTree; ENSGT00390000010169; -.
DR HOGENOM; CLU_022731_1_1_1; -.
DR InParanoid; Q9BUR4; -.
DR OMA; FTKGCQW; -.
DR OrthoDB; 934297at2759; -.
DR PhylomeDB; Q9BUR4; -.
DR TreeFam; TF315169; -.
DR PathwayCommons; Q9BUR4; -.
DR Reactome; R-HSA-171319; Telomere Extension By Telomerase.
DR Reactome; R-HSA-390471; Association of TriC/CCT with target proteins during biosynthesis.
DR SignaLink; Q9BUR4; -.
DR BioGRID-ORCS; 55135; 121 hits in 1086 CRISPR screens.
DR GenomeRNAi; 55135; -.
DR Pharos; Q9BUR4; Tbio.
DR PRO; PR:Q9BUR4; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9BUR4; protein.
DR Bgee; ENSG00000141499; Expressed in right uterine tube and 167 other tissues.
DR ExpressionAtlas; Q9BUR4; baseline and differential.
DR Genevisible; Q9BUR4; HS.
DR GO; GO:0015030; C:Cajal body; IDA:UniProtKB.
DR GO; GO:0000781; C:chromosome, telomeric region; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0035861; C:site of double-strand break; IDA:UniProtKB.
DR GO; GO:0005697; C:telomerase holoenzyme complex; IDA:UniProtKB.
DR GO; GO:0051087; F:chaperone binding; IPI:BHF-UCL.
DR GO; GO:0042393; F:histone binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:BHF-UCL.
DR GO; GO:0003723; F:RNA binding; IDA:UniProtKB.
DR GO; GO:0070034; F:telomerase RNA binding; IDA:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0030576; P:Cajal body organization; IMP:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0045739; P:positive regulation of DNA repair; IDA:UniProtKB.
DR GO; GO:2000781; P:positive regulation of double-strand break repair; IDA:UniProtKB.
DR GO; GO:1905168; P:positive regulation of double-strand break repair via homologous recombination; IDA:UniProtKB.
DR GO; GO:2001034; P:positive regulation of double-strand break repair via nonhomologous end joining; IDA:UniProtKB.
DR GO; GO:1904851; P:positive regulation of establishment of protein localization to telomere; IMP:BHF-UCL.
DR GO; GO:0051973; P:positive regulation of telomerase activity; IDA:UniProtKB.
DR GO; GO:1904867; P:protein localization to Cajal body; IDA:UniProtKB.
DR GO; GO:0034337; P:RNA folding; IDA:UniProtKB.
DR GO; GO:0090666; P:scaRNA localization to Cajal body; IDA:UniProtKB.
DR GO; GO:0090671; P:telomerase RNA localization to Cajal body; IMP:BHF-UCL.
DR GO; GO:0032203; P:telomere formation via telomerase; IMP:UniProtKB.
DR GO; GO:0007004; P:telomere maintenance via telomerase; IDA:UniProtKB.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR Pfam; PF00400; WD40; 2.
DR SMART; SM00320; WD40; 5.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS50082; WD_REPEATS_2; 2.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Chaperone; Chromosome; Disease variant; DNA damage;
KW DNA repair; Dyskeratosis congenita; Host-virus interaction; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; RNA-binding; Telomere;
KW WD repeat.
FT CHAIN 1..548
FT /note="Telomerase Cajal body protein 1"
FT /id="PRO_0000242696"
FT REPEAT 167..206
FT /note="WD 1"
FT /evidence="ECO:0000255"
FT REPEAT 222..267
FT /note="WD 2"
FT /evidence="ECO:0000255"
FT REPEAT 272..313
FT /note="WD 3"
FT /evidence="ECO:0000255"
FT REPEAT 323..364
FT /note="WD 4"
FT /evidence="ECO:0000255"
FT REPEAT 365..405
FT /note="WD 5"
FT /evidence="ECO:0000255"
FT REPEAT 411..450
FT /note="WD 6"
FT /evidence="ECO:0000255"
FT REGION 1..142
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 526..548
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 26
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 30
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 54
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18220336, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 64
FT /note="Phosphoserine; by ATM"
FT /evidence="ECO:0000269|PubMed:27715493,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 85
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:24275569"
FT MOD_RES 90
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:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 112
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 114
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 489
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 491
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 VARIANT 11
FT /note="P -> S (in dbSNP:rs17880282)"
FT /id="VAR_026865"
FT VARIANT 68
FT /note="R -> G (in dbSNP:rs2287499)"
FT /evidence="ECO:0000269|PubMed:21205863, ECO:0000269|Ref.3"
FT /id="VAR_026866"
FT VARIANT 136
FT /note="P -> R (in dbSNP:rs34067256)"
FT /id="VAR_057618"
FT VARIANT 164
FT /note="F -> L (in DKCB3; disrupts telomerase localization
FT to Cajal bodies resulting in misdirection of telomerase RNA
FT to nucleoli; dbSNP:rs281865547)"
FT /evidence="ECO:0000269|PubMed:21205863"
FT /id="VAR_065873"
FT VARIANT 187
FT /note="N -> T (in dbSNP:rs35762939)"
FT /id="VAR_057619"
FT VARIANT 376
FT /note="H -> Y (in DKCB3; shortened telomeres; disrupts
FT telomerase localization to Cajal bodies resulting in
FT misdirection of telomerase RNA to nucleoli;
FT dbSNP:rs281865549)"
FT /evidence="ECO:0000269|PubMed:21205863,
FT ECO:0000269|PubMed:21602826"
FT /id="VAR_065874"
FT VARIANT 398
FT /note="R -> W (in DKCB3; disrupts telomerase localization
FT to Cajal bodies resulting in misdirection of telomerase RNA
FT to nucleoli; dbSNP:rs281865548)"
FT /evidence="ECO:0000269|PubMed:21205863"
FT /id="VAR_065875"
FT VARIANT 435
FT /note="G -> R (in DKCB3; shortened telomeres; disrupts
FT telomerase localization to Cajal bodies resulting in
FT misdirection of telomerase RNA to nucleoli;
FT dbSNP:rs281865550)"
FT /evidence="ECO:0000269|PubMed:21205863,
FT ECO:0000269|PubMed:21602826"
FT /id="VAR_065876"
FT VARIANT 494
FT /note="E -> Q (in dbSNP:rs35123152)"
FT /id="VAR_057620"
FT VARIANT 522
FT /note="A -> G (in dbSNP:rs7640)"
FT /evidence="ECO:0000269|PubMed:21205863"
FT /id="VAR_026867"
FT MUTAGEN 64
FT /note="S->A: Abolished phosphorylation by ATM and impaired
FT ability to promote DNA repair."
FT /evidence="ECO:0000269|PubMed:27715493"
FT CONFLICT 21
FT /note="A -> V (in Ref. 2; BAA91579)"
FT /evidence="ECO:0000305"
FT CONFLICT 497
FT /note="E -> G (in Ref. 2; BAG51781)"
FT /evidence="ECO:0000305"
FT CONFLICT 526
FT /note="S -> G (in Ref. 2; BAG51781)"
FT /evidence="ECO:0000305"
FT STRAND 156..159
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 166..169
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 172..177
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 179..188
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 191..197
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 217..221
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 226..231
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 244..252
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 255..258
FT /evidence="ECO:0007829|PDB:7BGB"
FT TURN 259..261
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 264..267
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 273..275
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 281..285
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 291..295
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 300..307
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 328..333
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 335..338
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 340..344
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 349..352
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 354..356
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 359..363
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 373..375
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 382..384
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 390..394
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 397..399
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 406..408
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 413..415
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 419..421
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 428..430
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 432..435
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 467..469
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 471..474
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 476..479
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 506..509
FT /evidence="ECO:0007829|PDB:7BGB"
SQ SEQUENCE 548 AA; 59309 MW; 4687517268A813B5 CRC64;
MKTLETQPLA PDCCPSDQDP APAHPSPHAS PMNKNADSEL MPPPPERGDP PRLSPDPVAG
SAVSQELREG DPVSLSTPLE TEFGSPSELS PRIEEQELSE NTSLPAEEAN GSLSEEEANG
PELGSGKAME DTSGEPAAED EGDTAWNYSF SQLPRFLSGS WSEFSTQPEN FLKGCKWAPD
GSCILTNSAD NILRIYNLPP ELYHEGEQVE YAEMVPVLRM VEGDTIYDYC WYSLMSSAQP
DTSYVASSSR ENPIHIWDAF TGELRASFRA YNHLDELTAA HSLCFSPDGS QLFCGFNRTV
RVFSTARPGR DCEVRATFAK KQGQSGIISC IAFSPAQPLY ACGSYGRSLG LYAWDDGSPL
ALLGGHQGGI THLCFHPDGN RFFSGARKDA ELLCWDLRQS GYPLWSLGRE VTTNQRIYFD
LDPTGQFLVS GSTSGAVSVW DTDGPGNDGK PEPVLSFLPQ KDCTNGVSLH PSLPLLATAS
GQRVFPEPTE SGDEGEELGL PLLSTRHVHL ECRLQLWWCG GAPDSSIPDD HQGEKGQGGT
EGGVGELI
