TERT_HUMAN
ID TERT_HUMAN Reviewed; 1132 AA.
AC O14746; O14783; Q2XS35; Q8N6C3; Q8NG38; Q8NG46;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 200.
DE RecName: Full=Telomerase reverse transcriptase;
DE EC=2.7.7.49 {ECO:0000269|PubMed:21602826, ECO:0000269|PubMed:29695869};
DE AltName: Full=HEST2;
DE AltName: Full=Telomerase catalytic subunit;
DE AltName: Full=Telomerase-associated protein 2;
DE Short=TP2;
GN Name=TERT; Synonyms=EST2, TCS1, TRT;
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).
RX PubMed=9288757; DOI=10.1016/s0092-8674(00)80538-3;
RA Meyerson M., Counter C.M., Eaton E.N., Ellisen L.W., Steiner P.,
RA Caddle S.D., Ziaugra L., Beijersbergen R.L., Davidoff M.J., Liu Q.,
RA Bacchetti S., Haber D.A., Weinberg R.A.;
RT "hEST2, the putative human telomerase catalytic subunit gene, is up-
RT regulated in tumor cells and during immortalization.";
RL Cell 90:785-795(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Embryonic kidney;
RX PubMed=9252327; DOI=10.1126/science.277.5328.955;
RA Nakamura T.M., Morin G.B., Chapman K.B., Weinrich S.L., Andrews W.H.,
RA Lingner J., Harley C.B., Cech T.R.;
RT "Telomerase catalytic subunit homologs from fission yeast and human.";
RL Science 277:955-959(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10333526; DOI=10.1016/s0378-1119(99)00108-0;
RA Wick M., Zubov D., Hagen G.;
RT "Genomic organization and promoter characterization of the gene encoding
RT the human telomerase reverse transcriptase (hTERT).";
RL Gene 232:97-106(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=12869302; DOI=10.1016/s1476-5586(03)80051-9;
RA Hisatomi H., Ohyashiki K., Ohyashiki J.H., Nagao K., Kanamaru T.,
RA Hirata H., Hibi N., Tsukada Y.;
RT "Expression profile of a gamma-deletion variant of the human telomerase
RT reverse transcriptase gene.";
RL Neoplasia 5:193-197(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4).
RC TISSUE=Stomach cancer;
RX PubMed=14654914;
RA Nagao K., Katsumata K., Aizawa Y., Saito N., Hirata H., Sasaki H.,
RA Yamamoto S., Hikiji K., Koiwa T., Hisatomi H.;
RT "Differential alternative splicing expressions of telomerase reverse
RT transcriptase in gastrointestinal cell lines.";
RL Oncol. Rep. 11:127-131(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Londono-Vallejo J.A.;
RT "Sequence of a BAC carrying the entire hTERT gene.";
RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS TYR-412 AND THR-1062.
RG NIEHS SNPs program;
RL Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 [10]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=8676067; DOI=10.1084/jem.183.6.2471;
RA Weng N.P., Levine B.L., June C.H., Hodes R.J.;
RT "Regulated expression of telomerase activity in human T lymphocyte
RT development and activation.";
RL J. Exp. Med. 183:2471-2479(1996).
RN [11]
RP FUNCTION IN TELOMERASE ACTIVITY, TISSUE SPECIFICITY, ASSOCIATION WITH TEP1,
RP AND MUTAGENESIS OF ASP-712; ASP-868 AND ASP-869.
RX PubMed=9389643; DOI=10.1101/gad.11.23.3109;
RA Harrington L., Zhou W., McPhail T., Oulton R., Yeung D.S., Mar V.,
RA Bass M.B., Robinson M.O.;
RT "Human telomerase contains evolutionarily conserved catalytic and
RT structural subunits.";
RL Genes Dev. 11:3109-3115(1997).
RN [12]
RP RECONSTITUTION OF THE TELOMERASE COMPLEX, AND MUTAGENESIS OF ASP-712;
RP ASP-868 AND ASP-869.
RX PubMed=9443919; DOI=10.1016/s0960-9822(98)70067-3;
RA Beattie T.L., Zhou W., Robinson M.O., Harrington L.;
RT "Reconstitution of human telomerase activity in vitro.";
RL Curr. Biol. 8:177-180(1998).
RN [13]
RP ASSOCIATION WITH TEP1.
RX PubMed=11029039; DOI=10.1091/mbc.11.10.3329;
RA Beattie T.L., Zhou W., Robinson M.O., Harrington L.;
RT "Polymerization defects within human telomerase are distinct from
RT telomerase RNA and TEP1 binding.";
RL Mol. Biol. Cell 11:3329-3340(2000).
RN [14]
RP INTERACTION WITH HSPA1A; HSP90A AND PTGES3.
RX PubMed=11274138; DOI=10.1074/jbc.c100055200;
RA Forsythe H.L., Jarvis J.L., Turner J.W., Elmore L.W., Holt S.E.;
RT "Stable association of hsp90 and p23, but Not hsp70, with active human
RT telomerase.";
RL J. Biol. Chem. 276:15571-15574(2001).
RN [15]
RP PHOSPHORYLATION AT TYR-707, SUBCELLULAR LOCATION, INTERACTION WITH RAN AND
RP XP01, AND MUTAGENESIS OF TYR-707.
RX PubMed=12808100; DOI=10.1128/mcb.23.13.4598-4610.2003;
RA Haendeler J., Hoffmann J., Brandes R.P., Zeiher A.M., Dimmeler S.;
RT "Hydrogen peroxide triggers nuclear export of telomerase reverse
RT transcriptase via Src kinase family-dependent phosphorylation of tyrosine
RT 707.";
RL Mol. Cell. Biol. 23:4598-4610(2003).
RN [16]
RP INTERACTION WITH MCRS1.
RX PubMed=15044100; DOI=10.1016/j.bbrc.2004.02.166;
RA Song H., Li Y., Chen G., Xing Z., Zhao J., Yokoyama K.K., Li T., Zhao M.;
RT "Human MCRS2, a cell-cycle-dependent protein, associates with LPTS/PinX1
RT and reduces the telomere length.";
RL Biochem. Biophys. Res. Commun. 316:1116-1123(2004).
RN [17]
RP SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=14963003; DOI=10.1161/01.res.0000121104.05977.f3;
RA Haendeler J., Hoffmann J., Diehl J.F., Vasa M., Spyridopoulos I.,
RA Zeiher A.M., Dimmeler S.;
RT "Antioxidants inhibit nuclear export of telomerase reverse transcriptase
RT and delay replicative senescence of endothelial cells.";
RL Circ. Res. 94:768-775(2004).
RN [18]
RP SUBCELLULAR LOCATION.
RX PubMed=15138842; DOI=10.1007/s00418-004-0645-5;
RA Yan P., Benhattar J., Seelentag W., Stehle J.C., Bosman F.T.;
RT "Immunohistochemical localization of hTERT protein in human tissues.";
RL Histochem. Cell Biol. 121:391-397(2004).
RN [19]
RP INTERACTION WITH NCL, AND SUBCELLULAR LOCATION.
RX PubMed=15371412; DOI=10.1074/jbc.m407643200;
RA Khurts S., Masutomi K., Delgermaa L., Arai K., Oishi N., Mizuno H.,
RA Hayashi N., Hahn W.C., Murakami S.;
RT "Nucleolin interacts with telomerase.";
RL J. Biol. Chem. 279:51508-51515(2004).
RN [20]
RP FUNCTIONAL DOMAINS, AND MUTAGENESIS OF TRP-547 AND ASP-868.
RX PubMed=15082768; DOI=10.1128/mcb.24.9.3720-3733.2004;
RA Moriarty T.J., Marie-Egyptienne D.T., Autexier C.;
RT "Functional organization of repeat addition processivity and DNA synthesis
RT determinants in the human telomerase multimer.";
RL Mol. Cell. Biol. 24:3720-3733(2004).
RN [21]
RP INTERACTION WITH MKRN1, AND UBIQUITINATION.
RX PubMed=15805468; DOI=10.1101/gad.1289405;
RA Kim J.H., Park S.-M., Kang M.R., Oh S.-Y., Lee T.H., Muller M.T.,
RA Chung I.K.;
RT "Ubiquitin ligase MKRN1 modulates telomere length homeostasis through a
RT proteolysis of hTERT.";
RL Genes Dev. 19:776-781(2005).
RN [22]
RP FUNCTION, AND MUTAGENESIS OF ASP-868.
RX PubMed=15857955; DOI=10.1091/mbc.e05-02-0148;
RA Moriarty T.J., Ward R.J., Taboski M.A., Autexier C.;
RT "An anchor site-type defect in human telomerase that disrupts telomere
RT length maintenance and cellular immortalization.";
RL Mol. Biol. Cell 16:3152-3161(2005).
RN [23]
RP FUNCTION, AND MUTAGENESIS OF ARG-631; ASP-712 AND ASP-868.
RX PubMed=17026956; DOI=10.1016/j.bbrc.2006.09.125;
RA Rahman R., Mo L., Cui W.;
RT "Telomerase with mutated catalytic motifs has dominant negative effects on
RT telomerase activity and inhibits cell growth.";
RL Biochem. Biophys. Res. Commun. 350:796-802(2006).
RN [24]
RP PHOSPHORYLATION, AND FUNCTION.
RX PubMed=17548608; DOI=10.4049/jimmunol.178.12.7710;
RA Plunkett F.J., Franzese O., Finney H.M., Fletcher J.M., Belaramani L.L.,
RA Salmon M., Dokal I., Webster D., Lawson A.D., Akbar A.N.;
RT "The loss of telomerase activity in highly differentiated CD8+CD28-CD27- T
RT cells is associated with decreased Akt (Ser473) phosphorylation.";
RL J. Immunol. 178:7710-7719(2007).
RN [25]
RP INTERACTION WITH NAT10.
RX PubMed=18082603; DOI=10.1016/j.molcel.2007.09.023;
RA Fu D., Collins K.;
RT "Purification of human telomerase complexes identifies factors involved in
RT telomerase biogenesis and telomere length regulation.";
RL Mol. Cell 28:773-785(2007).
RN [26]
RP FUNCTION, DNA-BINDING, AND MUTAGENESIS OF 137-TRP--LEU-141; ASP-712 AND
RP 930-TRP--LEU-934.
RX PubMed=17296728; DOI=10.1128/mcb.02368-06;
RA Wyatt H.D., Lobb D.A., Beattie T.L.;
RT "Characterization of physical and functional anchor site interactions in
RT human telomerase.";
RL Mol. Cell. Biol. 27:3226-3240(2007).
RN [27]
RP FUNCTION, AND MUTAGENESIS OF LEU-866 AND VAL-867.
RX PubMed=17264120; DOI=10.1093/nar/gkm002;
RA Drosopoulos W.C., Prasad V.R.;
RT "The active site residue Valine 867 in human telomerase reverse
RT transcriptase influences nucleotide incorporation and fidelity.";
RL Nucleic Acids Res. 35:1155-1168(2007).
RN [28]
RP INTERACTION WITH PTPN11, PHOSPHORYLATION AT TYR-707, SUBCELLULAR LOCATION,
RP AND MUTAGENESIS OF TYR-707.
RX PubMed=18829466; DOI=10.1074/jbc.m805138200;
RA Jakob S., Schroeder P., Lukosz M., Buchner N., Spyridopoulos I.,
RA Altschmied J., Haendeler J.;
RT "Nuclear protein tyrosine phosphatase Shp-2 is one important negative
RT regulator of nuclear export of telomerase reverse transcriptase.";
RL J. Biol. Chem. 283:33155-33161(2008).
RN [29]
RP PHOSPHORYLATION, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19188162; DOI=10.1158/1078-0432.ccr-08-0792;
RA Ram R., Uziel O., Eldan O., Fenig E., Beery E., Lichtenberg S.,
RA Nordenberg Y., Lahav M.;
RT "Ionizing radiation up-regulates telomerase activity in cancer cell lines
RT by post-translational mechanism via ras/phosphatidylinositol 3-kinase/Akt
RT pathway.";
RL Clin. Cancer Res. 15:914-923(2009).
RN [30]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PML.
RX PubMed=19567472; DOI=10.1242/jcs.048066;
RA Oh W., Ghim J., Lee E.W., Yang M.R., Kim E.T., Ahn J.H., Song J.;
RT "PML-IV functions as a negative regulator of telomerase by interacting with
RT TERT.";
RL J. Cell Sci. 122:2613-2622(2009).
RN [31]
RP INTERACTION WITH SMARCA4, AND FUNCTION.
RX PubMed=19571879; DOI=10.1038/nature08137;
RA Park J.I., Venteicher A.S., Hong J.Y., Choi J., Jun S., Shkreli M.,
RA Chang W., Meng Z., Cheung P., Ji H., McLaughlin M., Veenstra T.D.,
RA Nusse R., McCrea P.D., Artandi S.E.;
RT "Telomerase modulates Wnt signalling by association with target gene
RT chromatin.";
RL Nature 460:66-72(2009).
RN [32]
RP FUNCTION, DNA-BINDING, AND MUTAGENESIS OF GLN-169.
RX PubMed=19777057; DOI=10.1371/journal.pone.0007176;
RA Wyatt H.D., Tsang A.R., Lobb D.A., Beattie T.L.;
RT "Human telomerase reverse transcriptase (hTERT) Q169 is essential for
RT telomerase function in vitro and in vivo.";
RL PLoS ONE 4:E7176-E7176(2009).
RN [33]
RP IDENTIFICATION IN THE TELOMERASE HOLOENZYME COMPLEX.
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 [34]
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 [35]
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 [36]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH NVL.
RX PubMed=22226966; DOI=10.1016/j.bbrc.2011.12.101;
RA Her J., Chung I.K.;
RT "The AAA-ATPase NVL2 is a telomerase component essential for holoenzyme
RT assembly.";
RL Biochem. Biophys. Res. Commun. 417:1086-1092(2012).
RN [37]
RP PHOSPHORYLATION AT SER-227, SUBCELLULAR LOCATION, AND NUCLEAR LOCALIZATION
RP SIGNAL.
RX PubMed=22366458; DOI=10.1242/jcs.099267;
RA Chung J., Khadka P., Chung I.K.;
RT "Nuclear import of hTERT requires a bipartite nuclear localization signal
RT and Akt-mediated phosphorylation.";
RL J. Cell Sci. 125:2684-2697(2012).
RN [38]
RP PHOSPHORYLATION AT SER-457, UBIQUITINATION, AND MUTAGENESIS OF SER-457.
RX PubMed=23362280; DOI=10.1074/jbc.m112.416792;
RA Jung H.Y., Wang X., Jun S., Park J.I.;
RT "Dyrk2-associated EDD-DDB1-VprBP E3 ligase inhibits telomerase by TERT
RT degradation.";
RL J. Biol. Chem. 288:7252-7262(2013).
RN [39]
RP UBIQUITINATION.
RX PubMed=23612978; DOI=10.1074/jbc.m112.416735;
RA Wang X., Singh S., Jung H.Y., Yang G., Jun S., Sastry K.J., Park J.I.;
RT "HIV-1 Vpr protein inhibits telomerase activity via the EDD-DDB1-VPRBP E3
RT ligase complex.";
RL J. Biol. Chem. 288:15474-15480(2013).
RN [40]
RP INVOLVEMENT IN CMM9.
RX PubMed=23348503; DOI=10.1126/science.1230062;
RA Horn S., Figl A., Rachakonda P.S., Fischer C., Sucker A., Gast A.,
RA Kadel S., Moll I., Nagore E., Hemminki K., Schadendorf D., Kumar R.;
RT "TERT promoter mutations in familial and sporadic melanoma.";
RL Science 339:959-961(2013).
RN [41]
RP INTERACTION WITH ATF7.
RX PubMed=29490055; DOI=10.1093/nar/gky155;
RA Maekawa T., Liu B., Nakai D., Yoshida K., Nakamura K.I., Yasukawa M.,
RA Koike M., Takubo K., Chatton B., Ishikawa F., Masutomi K., Ishii S.;
RT "ATF7 mediates TNF-alpha-induced telomere shortening.";
RL Nucleic Acids Res. 46:4487-4504(2018).
RN [42]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 461-469 IN COMPLEX WITH CLASS I
RP MAJOR HISTOCOMPATIBILITY COMPLEX (MHC).
RX PubMed=16323248; DOI=10.1002/eji.200535424;
RA Cole D.K., Rizkallah P.J., Gao F., Watson N.I., Boulter J.M., Bell J.I.,
RA Sami M., Gao G.F., Jakobsen B.K.;
RT "Crystal structure of HLA-A*2402 complexed with a telomerase peptide.";
RL Eur. J. Immunol. 36:170-179(2006).
RN [43]
RP STRUCTURE BY ELECTRON MICROSCOPY (7.7 ANGSTROMS) OF THE TELOMERASE
RP HOLOENZYME COMPLEX, AND CATALYTIC ACTIVITY.
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 [44]
RP VARIANT AA THR-202, VARIANTS DKCA2 TRP-979 AND LEU-1127, CHARACTERIZATION
RP OF VARIANT AA THR-202, AND CHARACTERIZATION OF VARIANTS DKCA2 TRP-979 AND
RP LEU-1127.
RX PubMed=15885610; DOI=10.1016/j.bcmd.2004.12.008;
RA Vulliamy T.J., Walne A., Baskaradas A., Mason P.J., Marrone A., Dokal I.;
RT "Mutations in the reverse transcriptase component of telomerase (TERT) in
RT patients with bone marrow failure.";
RL Blood Cells Mol. Dis. 34:257-263(2005).
RN [45]
RP VARIANTS PFBMFT1 THR-202; TYR-412; MET-694; CYS-772 AND MET-1090, AND
RP VARIANTS THR-279; GLU-441 DEL AND THR-1062.
RX PubMed=15814878; DOI=10.1056/nejmoa042980;
RA Yamaguchi H., Calado R.T., Ly H., Kajigaya S., Baerlocher G.M.,
RA Chanock S.J., Lansdorp P.M., Young N.S.;
RT "Mutations in TERT, the gene for telomerase reverse transcriptase, in
RT aplastic anemia.";
RL N. Engl. J. Med. 352:1413-1424(2005).
RN [46]
RP VARIANT DKCA2 ASN-902, AND CHARACTERIZATION OF VARIANT DKCA2 ASN-902.
RX PubMed=16247010; DOI=10.1073/pnas.0508124102;
RA Armanios M., Chen J.-L., Chang Y.-P.C., Brodsky R.A., Hawkins A.,
RA Griffin C.A., Eshleman J.R., Cohen A.R., Chakravarti A., Hamosh A.,
RA Greider C.W.;
RT "Haploinsufficiency of telomerase reverse transcriptase leads to
RT anticipation in autosomal dominant dyskeratosis congenita.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:15960-15964(2005).
RN [47]
RP INVOLVEMENT IN CAD SUSCEPTIBILITY.
RX PubMed=16890917; DOI=10.1016/j.bbrc.2006.07.103;
RA Matsubara Y., Murata M., Watanabe K., Saito I., Miyaki K., Omae K.,
RA Ishikawa M., Matsushita K., Iwanaga S., Ogawa S., Ikeda Y.;
RT "Coronary artery disease and a functional polymorphism of hTERT.";
RL Biochem. Biophys. Res. Commun. 348:669-672(2006).
RN [48]
RP VARIANT DKCB4 ARG-721.
RX PubMed=16332973; DOI=10.1182/blood-2005-07-2622;
RA Vulliamy T.J., Marrone A., Knight S.W., Walne A., Mason P.J., Dokal I.;
RT "Mutations in dyskeratosis congenita: their impact on telomere length and
RT the diversity of clinical presentation.";
RL Blood 107:2680-2685(2006).
RN [49]
RP VARIANTS AA ASP-682 AND MET-726, AND CHARACTERIZATION OF VARIANT AA
RP MET-726.
RX PubMed=16627250;
RA Liang J., Yagasaki H., Kamachi Y., Hama A., Matsumoto K., Kato K., Kudo K.,
RA Kojima S.;
RT "Mutations in telomerase catalytic protein in Japanese children with
RT aplastic anemia.";
RL Haematologica 91:656-658(2006).
RN [50]
RP VARIANT AA ASN-570, AND CHARACTERIZATION OF VARIANTS ASN-570; ASP-682;
RP ARG-721; MET-726; ASN-902; TRP-979 AND LEU-1127.
RX PubMed=16990594; DOI=10.1182/blood-2006-07-035089;
RA Xin Z.T., Beauchamp A.D., Calado R.T., Bradford J.W., Regal J.A.,
RA Shenoy A., Liang Y., Lansdorp P.M., Young N.S., Ly H.;
RT "Functional characterization of natural telomerase mutations found in
RT patients with hematologic disorders.";
RL Blood 109:524-532(2007).
RN [51]
RP VARIANTS DKCB4 CYS-811 AND TRP-901, AND CHARACTERIZATION OF VARIANTS DKCB4
RP CYS-811 AND TRP-901.
RX PubMed=17785587; DOI=10.1182/blood-2006-12-062851;
RA Marrone A., Walne A., Tamary H., Masunari Y., Kirwan M., Beswick R.,
RA Vulliamy T., Dokal I.;
RT "Telomerase reverse-transcriptase homozygous mutations in autosomal
RT recessive dyskeratosis congenita and Hoyeraal-Hreidarsson syndrome.";
RL Blood 110:4198-4205(2007).
RN [52]
RP VARIANTS PFBMFT1 GLN-55 AND MET-1110, AND CHARACTERIZATION OF VARIANTS
RP PFBMFT1 GLN-55 AND MET-1110.
RX PubMed=17392301; DOI=10.1056/nejmoa066157;
RA Armanios M.Y., Chen J.J., Cogan J.D., Alder J.K., Ingersoll R.G.,
RA Markin C., Lawson W.E., Xie M., Vulto I., Phillips J.A., Lansdorp P.M.,
RA Greider C.W., Loyd J.E.;
RT "Telomerase mutations in families with idiopathic pulmonary fibrosis.";
RL N. Engl. J. Med. 356:1317-1326(2007).
RN [53]
RP VARIANT PFBMFT1 HIS-865.
RX PubMed=17460043; DOI=10.1073/pnas.0701009104;
RA Tsakiri K.D., Cronkhite J.T., Kuan P.J., Xing C., Raghu G., Weissler J.C.,
RA Rosenblatt R.L., Shay J.W., Garcia C.K.;
RT "Adult-onset pulmonary fibrosis caused by mutations in telomerase.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:7552-7557(2007).
RN [54]
RP VARIANTS DKCB4 TYR-412 AND SER-704, AND CHARACTERIZATION OF VARIANTS DKCB4
RP TYR-412 AND SER-704.
RX PubMed=18042801; DOI=10.1182/blood-2007-10-120907;
RA Du H.Y., Pumbo E., Manley P., Field J.J., Bayliss S.J., Wilson D.B.,
RA Mason P.J., Bessler M.;
RT "Complex inheritance pattern of dyskeratosis congenita in two families with
RT 2 different mutations in the telomerase reverse transcriptase gene.";
RL Blood 111:1128-1130(2008).
RN [55]
RP VARIANTS ALA-65; MET-299; LYS-522 AND THR-1062, AND VARIANTS AA THR-202;
RP TYR-412; GLU-441 DEL; ASN-570; GLN-631; MET-694 AND LEU-785.
RX PubMed=19760749; DOI=10.1002/humu.21115;
RA Kirwan M., Vulliamy T., Marrone A., Walne A.J., Beswick R., Hillmen P.,
RA Kelly R., Stewart A., Bowen D., Schonland S.O., Whittle A.M., McVerry A.,
RA Gilleece M., Dokal I.;
RT "Defining the pathogenic role of telomerase mutations in myelodysplastic
RT syndrome and acute myeloid leukemia.";
RL Hum. Mutat. 30:1567-1573(2009).
RN [56]
RP VARIANTS ALA-65; MET-299; TYR-412; GLU-441 DEL; LYS-522 AND THR-1062.
RX PubMed=19147845; DOI=10.1073/pnas.0807057106;
RA Calado R.T., Regal J.A., Hills M., Yewdell W.T., Dalmazzo L.F., Zago M.A.,
RA Lansdorp P.M., Hogge D., Chanock S.J., Estey E.H., Falcao R.P., Young N.S.;
RT "Constitutional hypomorphic telomerase mutations in patients with acute
RT myeloid leukemia.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:1187-1192(2009).
RN [57]
RP VARIANTS PFBMFT1 MET-170; THR-716; PHE-841; ARG-902 AND PHE-1025, AND
RP CHARACTERIZATION OF VARIANTS PFBMFT1 MET-170; THR-716; PHE-841 AND
RP PHE-1025.
RX PubMed=21436073; DOI=10.1182/blood-2010-11-322149;
RA Parry E.M., Alder J.K., Qi X., Chen J.J., Armanios M.;
RT "Syndrome complex of bone marrow failure and pulmonary fibrosis predicts
RT germline defects in telomerase.";
RL Blood 117:5607-5611(2011).
RN [58]
RP VARIANT DKCB4 SER-704, VARIANT DKCA2 TRP-979, CHARACTERIZATION OF VARIANT
RP DKCB4 SER-704, CHARACTERIZATION OF VARIANT DKCA2 TRP-979, AND CATALYTIC
RP ACTIVITY.
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 [59]
RP VARIANTS PFBMFT1 ILE-791 AND MET-867, AND CHARACTERIZATION OF VARIANTS
RP PFBMFT1 ILE-791 AND MET-867.
RX PubMed=21483807; DOI=10.1371/journal.pgen.1001352;
RA Alder J.K., Cogan J.D., Brown A.F., Anderson C.J., Lawson W.E.,
RA Lansdorp P.M., Phillips J.A. III, Loyd J.E., Chen J.J., Armanios M.;
RT "Ancestral mutation in telomerase causes defects in repeat addition
RT processivity and manifests as familial pulmonary fibrosis.";
RL PLoS Genet. 7:E1001352-E1001352(2011).
RN [60]
RP VARIANT PFBMFT1 LEU-923.
RX PubMed=22512499; DOI=10.1056/nejmc1200999;
RA Gansner J.M., Rosas I.O., Ebert B.L.;
RT "Pulmonary fibrosis, bone marrow failure, and telomerase mutation.";
RL N. Engl. J. Med. 366:1551-1553(2012).
RN [61]
RP VARIANTS PRO-381 AND THR-1062.
RX PubMed=31355908; DOI=10.1111/cge.13614;
RA Krenke K., Szczaluba K., Bielecka T., Rydzanicz M., Lange J., Koppolu A.,
RA Ploski R.;
RT "FARSA mutations mimic phenylalanyl-tRNA synthetase deficiency caused by
RT FARSB defects.";
RL Clin. Genet. 96:468-472(2019).
CC -!- FUNCTION: Telomerase is a ribonucleoprotein enzyme essential for the
CC replication of chromosome termini in most eukaryotes. Active in
CC progenitor and cancer cells. Inactive, or very low activity, in normal
CC somatic cells. Catalytic component of the teleromerase holoenzyme
CC complex whose main activity is the elongation of telomeres by acting as
CC a reverse transcriptase that adds simple sequence repeats to chromosome
CC ends by copying a template sequence within the RNA component of the
CC enzyme. Catalyzes the RNA-dependent extension of 3'-chromosomal termini
CC with the 6-nucleotide telomeric repeat unit, 5'-TTAGGG-3'. The
CC catalytic cycle involves primer binding, primer extension and release
CC of product once the template boundary has been reached or nascent
CC product translocation followed by further extension. More active on
CC substrates containing 2 or 3 telomeric repeats. Telomerase activity is
CC regulated by a number of factors including telomerase complex-
CC associated proteins, chaperones and polypeptide modifiers. Modulates
CC Wnt signaling. Plays important roles in aging and antiapoptosis.
CC {ECO:0000269|PubMed:14963003, ECO:0000269|PubMed:15082768,
CC ECO:0000269|PubMed:15857955, ECO:0000269|PubMed:17026956,
CC ECO:0000269|PubMed:17264120, ECO:0000269|PubMed:17296728,
CC ECO:0000269|PubMed:17548608, ECO:0000269|PubMed:19188162,
CC ECO:0000269|PubMed:19567472, ECO:0000269|PubMed:19571879,
CC ECO:0000269|PubMed:19777057, ECO:0000269|PubMed:9389643}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) =
CC diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339,
CC Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560,
CC ChEBI:CHEBI:173112; EC=2.7.7.49;
CC Evidence={ECO:0000269|PubMed:21602826, ECO:0000269|PubMed:29695869};
CC -!- SUBUNIT: Catalytic component of the telomerase holoenzyme complex
CC composed of one molecule of TERT, one molecule of WRAP53/TCAB1, two
CC molecules of H/ACA ribonucleoprotein complex subunits DKC1, NOP10, NHP2
CC and GAR1, and a telomerase RNA template component (TERC)
CC (PubMed:19179534, PubMed:20351177, PubMed:29695869). The telomerase
CC holoenzyme complex is associated with TEP1, SMG6/EST1A and POT1
CC (PubMed:19179534). The molecular chaperone HSP90/P23 complex is
CC required for correct assembly and stabilization of the active
CC telomerase (PubMed:11274138). Interacts directly with HSP90A and PTGES3
CC (PubMed:11274138). Interacts with HSPA1A; the interaction occurs in the
CC absence of TERC and dissociates once the complex has formed
CC (PubMed:11274138). Interacts with RAN; the interaction promotes nuclear
CC export of TERT (PubMed:12808100). Interacts with XPO1
CC (PubMed:12808100). Interacts with PTPN11; the interaction retains TERT
CC in the nucleus (PubMed:18829466). Interacts with NCL (via RRM1 and C-
CC terminal RRM4/Arg/Gly-rich domains); the interaction is important for
CC nucleolar localization of TERT (PubMed:15371412). Interacts with
CC SMARCA4 (via the bromodomain); the interaction regulates Wnt-mediated
CC signaling (By similarity). Interacts with MCRS1 (isoform MCRS2); the
CC interaction inhibits in vitro telomerase activity (PubMed:15044100).
CC Interacts with PIF1; the interaction has no effect on the elongation
CC activity of TERT (By similarity). Interacts with PML; the interaction
CC recruits TERT to PML bodies and inhibits telomerase activity
CC (PubMed:19567472). Interacts with GNL3L (By similarity). Interacts with
CC isoform 1 and isoform 2 of NVL (PubMed:22226966). Interacts with DHX36
CC (PubMed:21846770). Interacts with ATF7 (PubMed:29490055).
CC {ECO:0000250|UniProtKB:O70372, ECO:0000269|PubMed:11274138,
CC ECO:0000269|PubMed:12808100, ECO:0000269|PubMed:15044100,
CC ECO:0000269|PubMed:15371412, ECO:0000269|PubMed:18829466,
CC ECO:0000269|PubMed:19179534, ECO:0000269|PubMed:19567472,
CC ECO:0000269|PubMed:20351177, ECO:0000269|PubMed:21846770,
CC ECO:0000269|PubMed:22226966, ECO:0000269|PubMed:29490055,
CC ECO:0000269|PubMed:29695869}.
CC -!- INTERACTION:
CC O14746; P35222: CTNNB1; NbExp=2; IntAct=EBI-1772203, EBI-491549;
CC O14746; Q9BVP2: GNL3; NbExp=3; IntAct=EBI-1772203, EBI-641642;
CC O14746; P06748: NPM1; NbExp=5; IntAct=EBI-1772203, EBI-78579;
CC O14746; Q96BK5: PINX1; NbExp=6; IntAct=EBI-1772203, EBI-721782;
CC O14746; P29590-5: PML; NbExp=7; IntAct=EBI-1772203, EBI-304008;
CC O14746; Q9Y265: RUVBL1; NbExp=11; IntAct=EBI-1772203, EBI-353675;
CC O14746; P51532: SMARCA4; NbExp=8; IntAct=EBI-1772203, EBI-302489;
CC O14746; O14746: TERT; NbExp=3; IntAct=EBI-1772203, EBI-1772203;
CC O14746; O14773-1: TPP1; NbExp=2; IntAct=EBI-1772203, EBI-15619703;
CC O14746; Q92900: UPF1; NbExp=3; IntAct=EBI-1772203, EBI-373471;
CC O14746; P03126: E6; Xeno; NbExp=7; IntAct=EBI-1772203, EBI-1177242;
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:22226966}.
CC Nucleus, nucleoplasm. Nucleus. Chromosome, telomere. Cytoplasm.
CC Nucleus, PML body. Note=Shuttling between nuclear and cytoplasm depends
CC on cell cycle, phosphorylation states, transformation and DNA damage.
CC Diffuse localization in the nucleoplasm. Enriched in nucleoli of
CC certain cell types. Translocated to the cytoplasm via nuclear pores in
CC a CRM1/RAN-dependent manner involving oxidative stress-mediated
CC phosphorylation at Tyr-707. Dephosphorylation at this site by SHP2
CC retains TERT in the nucleus. Translocated to the nucleus by
CC phosphorylation by AKT.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=O14746-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O14746-2; Sequence=VSP_019587, VSP_019588;
CC Name=3;
CC IsoId=O14746-3; Sequence=VSP_021727;
CC Name=4;
CC IsoId=O14746-4; Sequence=VSP_053369, VSP_019587, VSP_019588;
CC -!- TISSUE SPECIFICITY: Expressed at a high level in thymocyte
CC subpopulations, at an intermediate level in tonsil T-lymphocytes, and
CC at a low to undetectable level in peripheral blood T-lymphocytes.
CC {ECO:0000269|PubMed:8676067, ECO:0000269|PubMed:9389643}.
CC -!- INDUCTION: Activated by cytotoxic events and down-regulated during
CC aging. In peripheral T-lymphocytes, induced By CD3 and by
CC PMA/ionomycin. Inhibited by herbimycin B. {ECO:0000269|PubMed:8676067}.
CC -!- DOMAIN: The primer grip sequence in the RT domain is required for
CC telomerase activity and for stable association with short telomeric
CC primers.
CC -!- DOMAIN: The RNA-interacting domain 1 (RD1)/N-terminal extension (NTE)
CC is required for interaction with the pseudoknot-template domain of each
CC of TERC dimers. It contains anchor sites that bind primer nucleotides
CC upstream of the RNA-DNA hybrid and is thus an essential determinant of
CC repeat addition processivity.
CC -!- DOMAIN: The RNA-interacting domain 2 (RD2) is essential for both
CC interaction with the CR4-CR5 domain of TERC and for DNA synthesis.
CC -!- PTM: Phosphorylation at Tyr-707 under oxidative stress leads to
CC translocation of TERT to the cytoplasm and reduces its antiapoptotic
CC activity. Dephosphorylated by SHP2/PTPN11 leading to nuclear retention.
CC Phosphorylation at Ser-227 by the AKT pathway promotes nuclear
CC location. Phosphorylation at the G2/M phase at Ser-457 by DYRK2
CC promotes ubiquitination by the EDVP complex and degradation.
CC {ECO:0000269|PubMed:12808100, ECO:0000269|PubMed:18829466,
CC ECO:0000269|PubMed:22366458, ECO:0000269|PubMed:23362280}.
CC -!- PTM: Ubiquitinated by the EDVP complex, a E3 ligase complex following
CC phosphorylation at Ser-457 by DYRK2. Ubiquitinated leads to proteasomal
CC degradation. {ECO:0000269|PubMed:23362280}.
CC -!- PTM: (Microbial infection) In case of infection by HIV-1, the EDVP
CC complex is hijacked by HIV-1 via interaction between HIV-1 Vpr and
CC DCAF1/VPRBP, leading to ubiquitination and degradation.
CC {ECO:0000269|PubMed:23362280}.
CC -!- DISEASE: Note=Activation of telomerase has been implicated in cell
CC immortalization and cancer cell pathogenesis.
CC -!- DISEASE: Aplastic anemia (AA) [MIM:609135]: A form of anemia in which
CC the bone marrow fails to produce adequate numbers of peripheral blood
CC elements. It is characterized by peripheral pancytopenia and marrow
CC hypoplasia. {ECO:0000269|PubMed:15885610, ECO:0000269|PubMed:16627250,
CC ECO:0000269|PubMed:16990594, ECO:0000269|PubMed:19760749}. Note=Disease
CC susceptibility is associated with variants affecting the gene
CC represented in this entry.
CC -!- DISEASE: Note=Genetic variations in TERT are associated with coronary
CC artery disease (CAD).
CC -!- DISEASE: Dyskeratosis congenita, autosomal dominant, 2 (DKCA2)
CC [MIM:613989]: 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:15885610, ECO:0000269|PubMed:16247010,
CC ECO:0000269|PubMed:21602826}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Pulmonary fibrosis, and/or bone marrow failure, telomere-
CC related, 1 (PFBMFT1) [MIM:614742]: An autosomal dominant disease
CC associated with shortened telomeres. Pulmonary fibrosis is the most
CC common manifestation. Other manifestations include aplastic anemia due
CC to bone marrow failure, hepatic fibrosis, and increased cancer risk,
CC particularly myelodysplastic syndrome and acute myeloid leukemia.
CC Phenotype, age at onset, and severity are determined by telomere
CC length. {ECO:0000269|PubMed:15814878, ECO:0000269|PubMed:17392301,
CC ECO:0000269|PubMed:17460043, ECO:0000269|PubMed:21436073,
CC ECO:0000269|PubMed:21483807, ECO:0000269|PubMed:22512499}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Dyskeratosis congenita, autosomal recessive, 4 (DKCB4)
CC [MIM:613989]: A severe form of dyskeratosis congenita, a rare
CC multisystem disorder caused by defective telomere maintenance. It is
CC characterized by progressive bone marrow failure, and the clinical
CC triad of reticulated skin hyperpigmentation, nail dystrophy, and
CC mucosal leukoplakia. Common but variable features include premature
CC graying, aplastic anemia, low platelets, osteoporosis, pulmonary
CC fibrosis, and liver fibrosis among others. Early mortality is often
CC associated with bone marrow failure, infections, fatal pulmonary
CC complications, or malignancy. {ECO:0000269|PubMed:16332973,
CC ECO:0000269|PubMed:17785587, ECO:0000269|PubMed:18042801,
CC ECO:0000269|PubMed:21602826}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Melanoma, cutaneous malignant 9 (CMM9) [MIM:615134]: A
CC malignant neoplasm of melanocytes, arising de novo or from a pre-
CC existing benign nevus, which occurs most often in the skin but also may
CC involve other sites. {ECO:0000269|PubMed:23348503}. Note=Disease
CC susceptibility is associated with variants affecting the gene
CC represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the reverse transcriptase family. Telomerase
CC subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/tert/";
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DR EMBL; AF018167; AAC51724.1; -; mRNA.
DR EMBL; AF015950; AAC51672.1; -; mRNA.
DR EMBL; AF128894; AAD30037.1; -; Genomic_DNA.
DR EMBL; AF128893; AAD30037.1; JOINED; Genomic_DNA.
DR EMBL; AB085628; BAC11010.1; -; mRNA.
DR EMBL; AB086379; BAC11014.1; -; mRNA.
DR EMBL; AB086950; BAC11015.1; -; mRNA.
DR EMBL; AY007685; AAG23289.1; -; Genomic_DNA.
DR EMBL; DQ264729; ABB72674.1; -; Genomic_DNA.
DR EMBL; AC114291; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471102; EAX08167.1; -; Genomic_DNA.
DR CCDS; CCDS3861.2; -. [O14746-1]
DR CCDS; CCDS54831.1; -. [O14746-3]
DR PIR; T03844; T03844.
DR RefSeq; NP_001180305.1; NM_001193376.1. [O14746-3]
DR RefSeq; NP_937983.2; NM_198253.2. [O14746-1]
DR PDB; 2BCK; X-ray; 2.80 A; C/F=461-469.
DR PDB; 4B18; X-ray; 2.52 A; B=222-240.
DR PDB; 4MNQ; X-ray; 2.74 A; C=540-548.
DR PDB; 5MEN; X-ray; 2.81 A; C=540-548.
DR PDB; 5MEO; X-ray; 1.77 A; C=540-548.
DR PDB; 5MEP; X-ray; 2.71 A; C/F=540-548.
DR PDB; 5MEQ; X-ray; 2.27 A; C=540-546.
DR PDB; 5MER; X-ray; 1.88 A; C/F=540-546.
DR PDB; 5UGW; X-ray; 2.31 A; A=961-1132.
DR PDB; 7BG9; EM; 3.80 A; A=1-1132.
DR PDB; 7QXA; EM; 3.20 A; A=1-1132.
DR PDB; 7QXB; EM; 3.91 A; A=1-1132.
DR PDB; 7QXS; EM; 3.91 A; A=1-1132.
DR PDB; 7V99; EM; 3.54 A; A=1-1132.
DR PDBsum; 2BCK; -.
DR PDBsum; 4B18; -.
DR PDBsum; 4MNQ; -.
DR PDBsum; 5MEN; -.
DR PDBsum; 5MEO; -.
DR PDBsum; 5MEP; -.
DR PDBsum; 5MEQ; -.
DR PDBsum; 5MER; -.
DR PDBsum; 5UGW; -.
DR PDBsum; 7BG9; -.
DR PDBsum; 7QXA; -.
DR PDBsum; 7QXB; -.
DR PDBsum; 7QXS; -.
DR PDBsum; 7V99; -.
DR AlphaFoldDB; O14746; -.
DR SMR; O14746; -.
DR BioGRID; 112874; 116.
DR ComplexPortal; CPX-17; Telomerase catalytic core complex.
DR ComplexPortal; CPX-20; TERT-RMRP complex.
DR ComplexPortal; CPX-265; Telomerase holoenzyme complex.
DR CORUM; O14746; -.
DR DIP; DIP-40646N; -.
DR ELM; O14746; -.
DR IntAct; O14746; 24.
DR MINT; O14746; -.
DR STRING; 9606.ENSP00000309572; -.
DR BindingDB; O14746; -.
DR ChEMBL; CHEMBL2916; -.
DR DrugBank; DB05036; Grn163l.
DR DrugBank; DB12747; Tertomotide.
DR DrugBank; DB00495; Zidovudine.
DR DrugCentral; O14746; -.
DR iPTMnet; O14746; -.
DR PhosphoSitePlus; O14746; -.
DR BioMuta; TERT; -.
DR EPD; O14746; -.
DR MassIVE; O14746; -.
DR PaxDb; O14746; -.
DR PeptideAtlas; O14746; -.
DR PRIDE; O14746; -.
DR ProteomicsDB; 48203; -. [O14746-1]
DR ProteomicsDB; 48204; -. [O14746-2]
DR ProteomicsDB; 48205; -. [O14746-3]
DR ProteomicsDB; 73418; -.
DR ABCD; O14746; 9 sequenced antibodies.
DR Antibodypedia; 8998; 1000 antibodies from 42 providers.
DR DNASU; 7015; -.
DR Ensembl; ENST00000310581.10; ENSP00000309572.5; ENSG00000164362.21. [O14746-1]
DR Ensembl; ENST00000334602.10; ENSP00000334346.6; ENSG00000164362.21. [O14746-3]
DR Ensembl; ENST00000460137.6; ENSP00000425003.1; ENSG00000164362.21. [O14746-4]
DR GeneID; 7015; -.
DR KEGG; hsa:7015; -.
DR MANE-Select; ENST00000310581.10; ENSP00000309572.5; NM_198253.3; NP_937983.2.
DR UCSC; uc003jcb.2; human. [O14746-1]
DR CTD; 7015; -.
DR DisGeNET; 7015; -.
DR GeneCards; TERT; -.
DR GeneReviews; TERT; -.
DR HGNC; HGNC:11730; TERT.
DR HPA; ENSG00000164362; Not detected.
DR MalaCards; TERT; -.
DR MIM; 187270; gene.
DR MIM; 609135; phenotype.
DR MIM; 613989; phenotype.
DR MIM; 614742; phenotype.
DR MIM; 615134; phenotype.
DR neXtProt; NX_O14746; -.
DR OpenTargets; ENSG00000164362; -.
DR Orphanet; 457246; Clear cell sarcoma of kidney.
DR Orphanet; 146; Differentiated thyroid carcinoma.
DR Orphanet; 1775; Dyskeratosis congenita.
DR Orphanet; 618; Familial melanoma.
DR Orphanet; 3322; Hoyeraal-Hreidarsson syndrome.
DR Orphanet; 88; Idiopathic aplastic anemia.
DR Orphanet; 2032; Idiopathic pulmonary fibrosis.
DR Orphanet; 2495; Meningioma.
DR PharmGKB; PA36447; -.
DR VEuPathDB; HostDB:ENSG00000164362; -.
DR eggNOG; KOG1005; Eukaryota.
DR GeneTree; ENSGT00390000018531; -.
DR HOGENOM; CLU_001996_2_0_1; -.
DR InParanoid; O14746; -.
DR OMA; FWLMDTY; -.
DR OrthoDB; 1297956at2759; -.
DR PhylomeDB; O14746; -.
DR TreeFam; TF329048; -.
DR PathwayCommons; O14746; -.
DR Reactome; R-HSA-171319; Telomere Extension By Telomerase.
DR Reactome; R-HSA-201722; Formation of the beta-catenin:TCF transactivating complex.
DR SignaLink; O14746; -.
DR SIGNOR; O14746; -.
DR BioGRID-ORCS; 7015; 22 hits in 1084 CRISPR screens.
DR EvolutionaryTrace; O14746; -.
DR GeneWiki; Telomerase_reverse_transcriptase; -.
DR GenomeRNAi; 7015; -.
DR Pharos; O14746; Tchem.
DR PRO; PR:O14746; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; O14746; protein.
DR Bgee; ENSG00000164362; Expressed in stromal cell of endometrium and 89 other tissues.
DR ExpressionAtlas; O14746; baseline and differential.
DR Genevisible; O14746; HS.
DR GO; GO:0000781; C:chromosome, telomeric region; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0042645; C:mitochondrial nucleoid; IDA:BHF-UCL.
DR GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR GO; GO:0000783; C:nuclear telomere cap complex; IC:BHF-UCL.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0031379; C:RNA-directed RNA polymerase complex; IPI:BHF-UCL.
DR GO; GO:0000333; C:telomerase catalytic core complex; IDA:BHF-UCL.
DR GO; GO:0005697; C:telomerase holoenzyme complex; IDA:UniProtKB.
DR GO; GO:1990572; C:TERT-RMRP complex; IDA:BHF-UCL.
DR GO; GO:0051087; F:chaperone binding; IPI:BHF-UCL.
DR GO; GO:0003677; F:DNA binding; IDA:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:BHF-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:BHF-UCL.
DR GO; GO:0047485; F:protein N-terminus binding; IPI:BHF-UCL.
DR GO; GO:0003723; F:RNA binding; IPI:BHF-UCL.
DR GO; GO:0003968; F:RNA-directed 5'-3' RNA polymerase activity; IDA:BHF-UCL.
DR GO; GO:0003964; F:RNA-directed DNA polymerase activity; IDA:BHF-UCL.
DR GO; GO:0003720; F:telomerase activity; IDA:UniProtKB.
DR GO; GO:0070034; F:telomerase RNA binding; IDA:BHF-UCL.
DR GO; GO:0003721; F:telomerase RNA reverse transcriptase activity; IDA:BHF-UCL.
DR GO; GO:0042162; F:telomeric DNA binding; IBA:GO_Central.
DR GO; GO:0098680; F:template-free RNA nucleotidyltransferase; IDA:BHF-UCL.
DR GO; GO:0001223; F:transcription coactivator binding; IPI:BHF-UCL.
DR GO; GO:0000049; F:tRNA binding; IDA:BHF-UCL.
DR GO; GO:0071456; P:cellular response to hypoxia; IMP:BHF-UCL.
DR GO; GO:0071897; P:DNA biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0022616; P:DNA strand elongation; IDA:BHF-UCL.
DR GO; GO:0062103; P:double-stranded RNA biosynthetic process; IDA:ARUK-UCL.
DR GO; GO:0070200; P:establishment of protein localization to telomere; IDA:BHF-UCL.
DR GO; GO:0007005; P:mitochondrion organization; IDA:BHF-UCL.
DR GO; GO:2000773; P:negative regulation of cellular senescence; IDA:BHF-UCL.
DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; IEA:Ensembl.
DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; IMP:BHF-UCL.
DR GO; GO:0010629; P:negative regulation of gene expression; IDA:BHF-UCL.
DR GO; GO:1903799; P:negative regulation of miRNA maturation; TAS:ARUK-UCL.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:1903704; P:negative regulation of siRNA production; IDA:BHF-UCL.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IEA:Ensembl.
DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0046326; P:positive regulation of glucose import; IEA:Ensembl.
DR GO; GO:0042635; P:positive regulation of hair cycle; ISS:BHF-UCL.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; IMP:BHF-UCL.
DR GO; GO:0051000; P:positive regulation of nitric-oxide synthase activity; IDA:BHF-UCL.
DR GO; GO:0032092; P:positive regulation of protein binding; IDA:BHF-UCL.
DR GO; GO:1904751; P:positive regulation of protein localization to nucleolus; IDA:BHF-UCL.
DR GO; GO:2000648; P:positive regulation of stem cell proliferation; ISS:BHF-UCL.
DR GO; GO:1903620; P:positive regulation of transdifferentiation; IEA:Ensembl.
DR GO; GO:1904754; P:positive regulation of vascular associated smooth muscle cell migration; IEA:Ensembl.
DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; IGI:BHF-UCL.
DR GO; GO:0031647; P:regulation of protein stability; IDA:BHF-UCL.
DR GO; GO:0090399; P:replicative senescence; IMP:BHF-UCL.
DR GO; GO:0046686; P:response to cadmium ion; IEA:Ensembl.
DR GO; GO:0006278; P:RNA-templated DNA biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0030422; P:siRNA processing; IDA:BHF-UCL.
DR GO; GO:0000723; P:telomere maintenance; TAS:UniProtKB.
DR GO; GO:0007004; P:telomere maintenance via telomerase; IDA:UniProtKB.
DR GO; GO:0001172; P:transcription, RNA-templated; IDA:BHF-UCL.
DR InterPro; IPR043502; DNA/RNA_pol_sf.
DR InterPro; IPR000477; RT_dom.
DR InterPro; IPR021891; Telomerase_RBD.
DR InterPro; IPR003545; Telomerase_RT.
DR PANTHER; PTHR12066; PTHR12066; 1.
DR Pfam; PF00078; RVT_1; 1.
DR Pfam; PF12009; Telomerase_RBD; 1.
DR PRINTS; PR01365; TELOMERASERT.
DR SMART; SM00975; Telomerase_RBD; 1.
DR SUPFAM; SSF56672; SSF56672; 1.
DR PROSITE; PS50878; RT_POL; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chromosome; Cytoplasm; Disease variant;
KW DNA-binding; Dyskeratosis congenita; Magnesium; Metal-binding;
KW Nucleotidyltransferase; Nucleus; Phosphoprotein; Reference proteome;
KW Ribonucleoprotein; RNA-directed DNA polymerase; Telomere; Transferase;
KW Ubl conjugation.
FT CHAIN 1..1132
FT /note="Telomerase reverse transcriptase"
FT /id="PRO_0000054925"
FT DOMAIN 605..935
FT /note="Reverse transcriptase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00405"
FT REGION 1..230
FT /note="RNA-interacting domain 1"
FT REGION 58..197
FT /note="GQ motif"
FT REGION 137..141
FT /note="Required for regulating specificity for telomeric
FT DNA and for processivity for primer elongation"
FT REGION 210..320
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 231..324
FT /note="Linker"
FT REGION 301..538
FT /note="Required for oligomerization"
FT REGION 325..550
FT /note="RNA-interacting domain 2"
FT REGION 376..521
FT /note="QFP motif"
FT REGION 397..417
FT /note="CP motif"
FT REGION 914..928
FT /note="Required for oligomerization"
FT REGION 930..934
FT /note="Primer grip sequence"
FT REGION 936..1132
FT /note="CTE"
FT MOTIF 222..240
FT /note="Bipartite nuclear localization signal"
FT MOTIF 328..333
FT /note="TFLY; involved in RNA binding"
FT /evidence="ECO:0000250|UniProtKB:Q4KTA7"
FT BINDING 712
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00405"
FT BINDING 868
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00405"
FT BINDING 869
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00405"
FT SITE 169
FT /note="Required for optimal binding of telomeric ssDNA and
FT incorporation of nucleotides at the second position of the
FT template"
FT SITE 867
FT /note="Required for nucleotide incorporation and primer
FT extension rate"
FT MOD_RES 227
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000269|PubMed:22366458"
FT MOD_RES 457
FT /note="Phosphoserine; by DYRK2"
FT /evidence="ECO:0000269|PubMed:23362280"
FT MOD_RES 707
FT /note="Phosphotyrosine; by SRC-type Tyr-kinases"
FT /evidence="ECO:0000269|PubMed:12808100,
FT ECO:0000269|PubMed:18829466"
FT VAR_SEQ 711..722
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14654914"
FT /id="VSP_053369"
FT VAR_SEQ 764..807
FT /note="STLTDLQPYMRQFVAHLQETSPLRDAVVIEQSSSLNEASSGLFD -> LRPV
FT PGDPAGLHPLHAALQPVLRRHGEQAVCGDSAGRAAPAFGG (in isoform 2 and
FT isoform 4)"
FT /evidence="ECO:0000303|PubMed:12869302,
FT ECO:0000303|PubMed:14654914"
FT /id="VSP_019587"
FT VAR_SEQ 808..1132
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:12869302,
FT ECO:0000303|PubMed:14654914"
FT /id="VSP_019588"
FT VAR_SEQ 885..947
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14654914"
FT /id="VSP_021727"
FT VARIANT 55
FT /note="L -> Q (in PFBMFT1; impaired telomerase activity;
FT dbSNP:rs387907247)"
FT /evidence="ECO:0000269|PubMed:17392301"
FT /id="VAR_062535"
FT VARIANT 65
FT /note="P -> A (associated with acute myeloid leukemia;
FT dbSNP:rs544215765)"
FT /evidence="ECO:0000269|PubMed:19147845,
FT ECO:0000269|PubMed:19760749"
FT /id="VAR_062780"
FT VARIANT 170
FT /note="V -> M (in PFBMFT1; the mutant protein is
FT demonstrated to cause decreased telomerase activity;
FT dbSNP:rs387907248)"
FT /evidence="ECO:0000269|PubMed:21436073"
FT /id="VAR_068792"
FT VARIANT 202
FT /note="A -> T (in PFBMFT1 and AA; severe and moderate;
FT associated with disease susceptibility; shorter telomeres;
FT dbSNP:rs121918661)"
FT /evidence="ECO:0000269|PubMed:15814878,
FT ECO:0000269|PubMed:15885610, ECO:0000269|PubMed:19760749"
FT /id="VAR_036863"
FT VARIANT 279
FT /note="A -> T (in dbSNP:rs61748181)"
FT /evidence="ECO:0000269|PubMed:15814878"
FT /id="VAR_036864"
FT VARIANT 299
FT /note="V -> M (associated with acute myeloid leukemia;
FT dbSNP:rs756624928)"
FT /evidence="ECO:0000269|PubMed:19147845,
FT ECO:0000269|PubMed:19760749"
FT /id="VAR_062781"
FT VARIANT 381
FT /note="R -> P (in dbSNP:rs777343359)"
FT /evidence="ECO:0000269|PubMed:31355908"
FT /id="VAR_084996"
FT VARIANT 412
FT /note="H -> Y (in PFBMFT1, AA and DKCB4; severe and
FT moderate; associated with susceptibility to acute
FT myelogenous leukemia; the mutant protein has 36% residual
FT activity; dbSNP:rs34094720)"
FT /evidence="ECO:0000269|PubMed:15814878,
FT ECO:0000269|PubMed:18042801, ECO:0000269|PubMed:19147845,
FT ECO:0000269|PubMed:19760749, ECO:0000269|Ref.7"
FT /id="VAR_025149"
FT VARIANT 441
FT /note="Missing (in AA; associated with susceptibility to
FT acute myeloid leukemia)"
FT /evidence="ECO:0000269|PubMed:15814878,
FT ECO:0000269|PubMed:19147845, ECO:0000269|PubMed:19760749"
FT /id="VAR_036865"
FT VARIANT 522
FT /note="R -> K (associated with acute myeloid leukemia)"
FT /evidence="ECO:0000269|PubMed:19147845,
FT ECO:0000269|PubMed:19760749"
FT /id="VAR_062782"
FT VARIANT 570
FT /note="K -> N (in AA; abolishes telomerase catalytic
FT activity but no effect on binding to TERC)"
FT /evidence="ECO:0000269|PubMed:16990594,
FT ECO:0000269|PubMed:19760749"
FT /id="VAR_062536"
FT VARIANT 631
FT /note="R -> Q (in AA; dbSNP:rs199422294)"
FT /evidence="ECO:0000269|PubMed:19760749"
FT /id="VAR_062783"
FT VARIANT 682
FT /note="G -> D (in AA; non-severe; abolishes telomerase
FT catalytic activity but little effect on binding to TERC;
FT dbSNP:rs199422295)"
FT /evidence="ECO:0000269|PubMed:16627250,
FT ECO:0000269|PubMed:16990594"
FT /id="VAR_062537"
FT VARIANT 694
FT /note="V -> M (in PFBMFT1 and AA; moderate;
FT dbSNP:rs121918662)"
FT /evidence="ECO:0000269|PubMed:15814878,
FT ECO:0000269|PubMed:19760749"
FT /id="VAR_036866"
FT VARIANT 704
FT /note="P -> S (in DKCB4; the mutant protein has 13%
FT residual activity; dbSNP:rs199422297)"
FT /evidence="ECO:0000269|PubMed:18042801,
FT ECO:0000269|PubMed:21602826"
FT /id="VAR_068793"
FT VARIANT 716
FT /note="A -> T (in PFBMFT1; the mutant protein is
FT demonstrated to cause severely compromised telomerase
FT activity; dbSNP:rs387907249)"
FT /evidence="ECO:0000269|PubMed:21436073"
FT /id="VAR_068794"
FT VARIANT 721
FT /note="P -> R (in DKCB4; no effect on telomerase catalytic
FT activity and little effect on binding to TERC;
FT dbSNP:rs199422299)"
FT /evidence="ECO:0000269|PubMed:16332973,
FT ECO:0000269|PubMed:16990594"
FT /id="VAR_062538"
FT VARIANT 726
FT /note="T -> M (in AA; very severe; no effect on telomerase
FT catalytic activity but shortened telomeres;
FT dbSNP:rs149566858)"
FT /evidence="ECO:0000269|PubMed:16627250,
FT ECO:0000269|PubMed:16990594"
FT /id="VAR_062539"
FT VARIANT 772
FT /note="Y -> C (in PFBMFT1; moderate; dbSNP:rs121918663)"
FT /evidence="ECO:0000269|PubMed:15814878"
FT /id="VAR_036867"
FT VARIANT 785
FT /note="P -> L (in AA; dbSNP:rs483352771)"
FT /evidence="ECO:0000269|PubMed:19760749"
FT /id="VAR_062784"
FT VARIANT 791
FT /note="V -> I (in PFBMFT1; associated with Met-867 in cis
FT on the same allele; the double mutant shows severe defects
FT in telomere repeat addition processivity;
FT dbSNP:rs141425941)"
FT /evidence="ECO:0000269|PubMed:21483807"
FT /id="VAR_068795"
FT VARIANT 811
FT /note="R -> C (in DKCB4; 50% reduction in telomerase
FT activity; dbSNP:rs199422301)"
FT /evidence="ECO:0000269|PubMed:17785587"
FT /id="VAR_062540"
FT VARIANT 841
FT /note="L -> F (in PFBMFT1)"
FT /evidence="ECO:0000269|PubMed:21436073"
FT /id="VAR_068796"
FT VARIANT 865
FT /note="R -> H (in PFBMFT1; dbSNP:rs121918666)"
FT /evidence="ECO:0000269|PubMed:17460043"
FT /id="VAR_036868"
FT VARIANT 867
FT /note="V -> M (in PFBMFT1; associated with Ile-791 in cis
FT on the same allele; the double mutant shows severe defects
FT in telomere repeat addition processivity; this mutation
FT causes most if not all of the functional defects;
FT dbSNP:rs201159197)"
FT /evidence="ECO:0000269|PubMed:21483807"
FT /id="VAR_068797"
FT VARIANT 901
FT /note="R -> W (in DKCB4; severe phenotype overlapping with
FT Hoyeraal-Hreidarsson syndrome; very short telomeres and
FT greatly reduced telomerase activity; dbSNP:rs199422304)"
FT /evidence="ECO:0000269|PubMed:17785587"
FT /id="VAR_062541"
FT VARIANT 902
FT /note="K -> N (in DKCA2; abolishes telomerase catalytic
FT activity but no effect on binding to TERC;
FT dbSNP:rs121918665)"
FT /evidence="ECO:0000269|PubMed:16247010,
FT ECO:0000269|PubMed:16990594"
FT /id="VAR_036869"
FT VARIANT 902
FT /note="K -> R (in PFBMFT1; dbSNP:rs387907250)"
FT /evidence="ECO:0000269|PubMed:21436073"
FT /id="VAR_068798"
FT VARIANT 923
FT /note="P -> L (in PFBMFT1; dbSNP:rs387907251)"
FT /evidence="ECO:0000269|PubMed:22512499"
FT /id="VAR_068799"
FT VARIANT 948
FT /note="S -> R (in dbSNP:rs34062885)"
FT /id="VAR_053726"
FT VARIANT 979
FT /note="R -> W (in DKCA2; shortened telomeres but no effect
FT on telomerase catalytic activity nor on binding to TERC;
FT dbSNP:rs199422305)"
FT /evidence="ECO:0000269|PubMed:15885610,
FT ECO:0000269|PubMed:16990594, ECO:0000269|PubMed:21602826"
FT /id="VAR_062542"
FT VARIANT 1025
FT /note="V -> F (in PFBMFT1)"
FT /evidence="ECO:0000269|PubMed:21436073"
FT /id="VAR_068800"
FT VARIANT 1062
FT /note="A -> T (increased incidence in sporadic acute
FT myeloid leukemia; dbSNP:rs35719940)"
FT /evidence="ECO:0000269|PubMed:15814878,
FT ECO:0000269|PubMed:19147845, ECO:0000269|PubMed:19760749,
FT ECO:0000269|PubMed:31355908, ECO:0000269|Ref.7"
FT /id="VAR_025150"
FT VARIANT 1090
FT /note="V -> M (in PFBMFT1; severe; dbSNP:rs121918664)"
FT /evidence="ECO:0000269|PubMed:15814878"
FT /id="VAR_036870"
FT VARIANT 1110
FT /note="T -> M (in PFBMFT1; unknown pathological
FT significance; impaired telomerase activity;
FT dbSNP:rs199422306)"
FT /evidence="ECO:0000269|PubMed:17392301"
FT /id="VAR_062543"
FT VARIANT 1127
FT /note="F -> L (in DKCA2; severe; shortened telomeres but no
FT effect on telomerase catalytic activity nor on binding to
FT TERC; dbSNP:rs1176273130)"
FT /evidence="ECO:0000269|PubMed:15885610,
FT ECO:0000269|PubMed:16990594"
FT /id="VAR_062544"
FT MUTAGEN 137..141
FT /note="WGLLL->AAAAA: Reduced catalytic activity and repeat
FT addition processivity. Complete loss of catalytic activity
FT but no loss of binding to telomeric primers; when
FT associated with 930-A--A-934."
FT /evidence="ECO:0000269|PubMed:17296728"
FT MUTAGEN 169
FT /note="Q->A: About 80% loss of enzymatic activity. Greatly
FT reduced incorporation of second nucleotide. Altered
FT strength of binding to ssDNA. Little effect on repeat
FT addition processivity, nor on TR interaction nor on protein
FT levels."
FT /evidence="ECO:0000269|PubMed:19777057"
FT MUTAGEN 169
FT /note="Q->N: About 85% loss of enzymatic activity. Greatly
FT reduced incorporation of second nucleotide. Altered
FT strength of binding to ssDNA. No effect on protein levels
FT nor on TR interaction."
FT /evidence="ECO:0000269|PubMed:19777057"
FT MUTAGEN 169
FT /note="Q->T: About 90% loss of enzymatic activity. Greatly
FT reduced incorporation of second nucleotide. Altered
FT strength of binding to ssDNA. No effect on protein levels
FT nor on TR interaction."
FT /evidence="ECO:0000269|PubMed:19777057"
FT MUTAGEN 457
FT /note="S->A: Abolishes phosphorylation by DYRK2."
FT /evidence="ECO:0000269|PubMed:23362280"
FT MUTAGEN 547
FT /note="W->A: Defective in high-affinity TERC interactions."
FT /evidence="ECO:0000269|PubMed:15082768"
FT MUTAGEN 631
FT /note="R->A: Abolishes telomerase catalytic activity."
FT /evidence="ECO:0000269|PubMed:17026956"
FT MUTAGEN 707
FT /note="Y->F: Abolishes oxidative stress-induced
FT phosphorylation and RAN binding. Impaired nuclear export
FT and enhanced antiapoptotic activity against ROS-dependent
FT apoptosis induction. Impaired interaction with PTPN11. No
FT dephosphorylation by PTPN11."
FT /evidence="ECO:0000269|PubMed:12808100,
FT ECO:0000269|PubMed:18829466"
FT MUTAGEN 712
FT /note="D->A: Loss of telomerase activity. In the absence of
FT TR, no loss of binding to telomeric primers."
FT /evidence="ECO:0000269|PubMed:17026956,
FT ECO:0000269|PubMed:17296728, ECO:0000269|PubMed:9389643,
FT ECO:0000269|PubMed:9443919"
FT MUTAGEN 866
FT /note="L->Y: Moderate reduction in telomerase activity, no
FT change in repeat extension rate nor on nucleotide
FT incorporation fidelity. Little further reduction in
FT activity but 13.5-fold increase in nucleotide incorporation
FT fidelity; when associated with M-867."
FT /evidence="ECO:0000269|PubMed:17264120"
FT MUTAGEN 867
FT /note="V->A: About 75% reduction in telomerase activity,
FT about 80% reduction in repeat reduction rate and 3.9-fold
FT increase in nucleotide incorporation fidelity."
FT /evidence="ECO:0000269|PubMed:17264120"
FT MUTAGEN 867
FT /note="V->M: About 75% reduction in telomerase activity,
FT about 50% reduction in repeat extension rate and 5.2-fold
FT increase in nucleotide incorporation fidelity. Little
FT further reduction in activity and 13.5-fold increase in
FT nucleotide incorporation fidelity; when associated with Y-
FT 866."
FT /evidence="ECO:0000269|PubMed:17264120"
FT MUTAGEN 867
FT /note="V->T: Severe reduction in telomerase activity, about
FT 50% reduction in repeat extension rate and 2.2-fold
FT increase in nucleotide incorporation fidelity. No further
FT reduction in activity but 2.8-fold increase in nucleotide
FT incorporation fidelity; when associated with Y-866."
FT /evidence="ECO:0000269|PubMed:17264120"
FT MUTAGEN 868..869
FT /note="DD->AA: Loss of telomerase activity."
FT MUTAGEN 868
FT /note="D->A: Loss of telomerase activity."
FT /evidence="ECO:0000269|PubMed:15082768,
FT ECO:0000269|PubMed:15857955, ECO:0000269|PubMed:17026956,
FT ECO:0000269|PubMed:9389643, ECO:0000269|PubMed:9443919"
FT MUTAGEN 869
FT /note="D->A: Loss of telomerase activity."
FT /evidence="ECO:0000269|PubMed:9389643,
FT ECO:0000269|PubMed:9443919"
FT MUTAGEN 930..934
FT /note="WCGLL->AAAAA: Completely abolishes telomerase-
FT mediated primer extension and reduced binding to short
FT telomeric primers. Complete loss of catalytic activity but
FT no further loss of binding to telomeric primers; when
FT associated with 137-A--A-141."
FT /evidence="ECO:0000269|PubMed:17296728"
FT CONFLICT 516
FT /note="D -> G (in Ref. 1; AAC51724)"
FT /evidence="ECO:0000305"
FT HELIX 966..983
FT /evidence="ECO:0007829|PDB:5UGW"
FT HELIX 984..986
FT /evidence="ECO:0007829|PDB:5UGW"
FT TURN 989..991
FT /evidence="ECO:0007829|PDB:5UGW"
FT HELIX 994..1017
FT /evidence="ECO:0007829|PDB:5UGW"
FT HELIX 1025..1027
FT /evidence="ECO:0007829|PDB:5UGW"
FT HELIX 1029..1050
FT /evidence="ECO:0007829|PDB:5UGW"
FT TURN 1051..1053
FT /evidence="ECO:0007829|PDB:5UGW"
FT HELIX 1067..1082
FT /evidence="ECO:0007829|PDB:5UGW"
FT HELIX 1083..1085
FT /evidence="ECO:0007829|PDB:5UGW"
FT HELIX 1086..1104
FT /evidence="ECO:0007829|PDB:5UGW"
FT HELIX 1111..1118
FT /evidence="ECO:0007829|PDB:5UGW"
SQ SEQUENCE 1132 AA; 126997 MW; 94E35469C4CA33A0 CRC64;
MPRAPRCRAV RSLLRSHYRE VLPLATFVRR LGPQGWRLVQ RGDPAAFRAL VAQCLVCVPW
DARPPPAAPS FRQVSCLKEL VARVLQRLCE RGAKNVLAFG FALLDGARGG PPEAFTTSVR
SYLPNTVTDA LRGSGAWGLL LRRVGDDVLV HLLARCALFV LVAPSCAYQV CGPPLYQLGA
ATQARPPPHA SGPRRRLGCE RAWNHSVREA GVPLGLPAPG ARRRGGSASR SLPLPKRPRR
GAAPEPERTP VGQGSWAHPG RTRGPSDRGF CVVSPARPAE EATSLEGALS GTRHSHPSVG
RQHHAGPPST SRPPRPWDTP CPPVYAETKH FLYSSGDKEQ LRPSFLLSSL RPSLTGARRL
VETIFLGSRP WMPGTPRRLP RLPQRYWQMR PLFLELLGNH AQCPYGVLLK THCPLRAAVT
PAAGVCAREK PQGSVAAPEE EDTDPRRLVQ LLRQHSSPWQ VYGFVRACLR RLVPPGLWGS
RHNERRFLRN TKKFISLGKH AKLSLQELTW KMSVRDCAWL RRSPGVGCVP AAEHRLREEI
LAKFLHWLMS VYVVELLRSF FYVTETTFQK NRLFFYRKSV WSKLQSIGIR QHLKRVQLRE
LSEAEVRQHR EARPALLTSR LRFIPKPDGL RPIVNMDYVV GARTFRREKR AERLTSRVKA
LFSVLNYERA RRPGLLGASV LGLDDIHRAW RTFVLRVRAQ DPPPELYFVK VDVTGAYDTI
PQDRLTEVIA SIIKPQNTYC VRRYAVVQKA AHGHVRKAFK SHVSTLTDLQ PYMRQFVAHL
QETSPLRDAV VIEQSSSLNE ASSGLFDVFL RFMCHHAVRI RGKSYVQCQG IPQGSILSTL
LCSLCYGDME NKLFAGIRRD GLLLRLVDDF LLVTPHLTHA KTFLRTLVRG VPEYGCVVNL
RKTVVNFPVE DEALGGTAFV QMPAHGLFPW CGLLLDTRTL EVQSDYSSYA RTSIRASLTF
NRGFKAGRNM RRKLFGVLRL KCHSLFLDLQ VNSLQTVCTN IYKILLLQAY RFHACVLQLP
FHQQVWKNPT FFLRVISDTA SLCYSILKAK NAGMSLGAKG AAGPLPSEAV QWLCHQAFLL
KLTRHRVTYV PLLGSLRTAQ TQLSRKLPGT TLTALEAAAN PALPSDFKTI LD
