EST1A_HUMAN
ID EST1A_HUMAN Reviewed; 1419 AA.
AC Q86US8; B7Z874; O94837; Q86VH6; Q9UF60;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 2.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Telomerase-binding protein EST1A {ECO:0000305};
DE EC=3.1.-.-;
DE AltName: Full=Ever shorter telomeres 1A {ECO:0000303|PubMed:12676087};
DE Short=hEST1A {ECO:0000303|PubMed:12676087};
DE AltName: Full=Nonsense mediated mRNA decay factor SMG6 {ECO:0000312|HGNC:HGNC:17809};
DE AltName: Full=Smg-6 homolog {ECO:0000312|HGNC:HGNC:17809};
DE AltName: Full=hSmg5/7a {ECO:0000303|PubMed:12554878};
GN Name=SMG6 {ECO:0000312|HGNC:HGNC:17809};
GN Synonyms=C17orf31 {ECO:0000312|HGNC:HGNC:17809},
GN EST1A {ECO:0000312|HGNC:HGNC:17809},
GN KIAA0732 {ECO:0000312|HGNC:HGNC:17809};
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), VARIANT THR-341, FUNCTION IN
RP TELOMERE REGULATION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND
RP IDENTIFICATION IN THE TELOMERASE RIBONUCLEOPROTEIN COMPLEX.
RC TISSUE=Cervix carcinoma;
RX PubMed=12676087; DOI=10.1016/s0960-9822(03)00173-8;
RA Reichenbach P., Hoess M., Azzalin C.M., Nabholz M., Bucher P., Lingner J.;
RT "A human homolog of yeast est1 associates with telomerase and uncaps
RT chromosome ends when overexpressed.";
RL Curr. Biol. 13:568-574(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS PRO-291
RP AND THR-341.
RC TISSUE=Brain;
RX PubMed=9872452; DOI=10.1093/dnares/5.5.277;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XI. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:277-286(1998).
RN [3]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 32-1419 (ISOFORM 1), FUNCTION IN TELOMERE
RP REGULATION, TISSUE SPECIFICITY, SINGLE-STRANDED TELOMERE DNA-BINDING,
RP IDENTIFICATION IN THE TELOMERASE RIBONUCLEOPROTEIN COMPLEX, AND INTERACTION
RP WITH TERT.
RX PubMed=12699629; DOI=10.1016/s0960-9822(03)00210-0;
RA Snow B.E., Erdmann N., Cruickshank J., Goldman H., Gill R.M.,
RA Robinson M.O., Harrington L.;
RT "Functional conservation of the telomerase protein Est1p in humans.";
RL Curr. Biol. 13:698-704(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Testis;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 888-1419 (ISOFORM 1).
RC TISSUE=Testis;
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 [10]
RP INTERACTION WITH PP2A CATALYTIC SUBUNITS; SMG1; UPF1; UPF2 AND UPF3B.
RX PubMed=12554878; DOI=10.1261/rna.2137903;
RA Chiu S.-Y., Serin G., Ohara O., Maquat L.E.;
RT "Characterization of human Smg5/7a: a protein with similarities to
RT Caenorhabditis elegans SMG5 and SMG7 that functions in the
RT dephosphorylation of Upf1.";
RL RNA 9:77-87(2003).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [12]
RP FUNCTION IN NONSENSE-MEDIATED MRNA DECAY, CATALYTIC ACTIVITY, DOMAIN, AND
RP MUTAGENESIS OF ASP-1251 AND ASP-1392.
RX PubMed=18974281; DOI=10.1261/rna.1386208;
RA Huntzinger E., Kashima I., Fauser M., Sauliere J., Izaurralde E.;
RT "SMG6 is the catalytic endonuclease that cleaves mRNAs containing nonsense
RT codons in metazoan.";
RL RNA 14:2609-2617(2008).
RN [13]
RP FUNCTION IN NONSENSE-MEDIATED MRNA DECAY, CATALYTIC ACTIVITY, DOMAIN,
RP SUBCELLULAR LOCATION, INTERACTION WITH UPF1, AND MUTAGENESIS OF ASP-1251;
RP ASP-1353 AND ASP-1392.
RX PubMed=19060897; DOI=10.1038/nsmb.1530;
RA Eberle A.B., Lykke-Andersen S., Muhlemann O., Jensen T.H.;
RT "SMG6 promotes endonucleolytic cleavage of nonsense mRNA in human cells.";
RL Nat. Struct. Mol. Biol. 16:49-55(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-479, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [15]
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 [16]
RP FUNCTION IN NONSENSE-MEDIATED MRNA DECAY, HOMOOLIGOMERIZATION, INTERACTION
RP WITH UPF1; UPF2; UPF3B; SMG5; SMG7 AND THE EXON JUNCTION COMPLEX, AND
RP MUTAGENESIS OF 46-ARG--TYR-52 AND 140-LYS--TYR-146.
RX PubMed=20930030; DOI=10.1101/gad.604610;
RA Kashima I., Jonas S., Jayachandran U., Buchwald G., Conti E., Lupas A.N.,
RA Izaurralde E.;
RT "SMG6 interacts with the exon junction complex via two conserved EJC-
RT binding motifs (EBMs) required for nonsense-mediated mRNA decay.";
RL Genes Dev. 24:2440-2450(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203; THR-479; SER-484;
RP SER-831; SER-870 AND SER-874, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [19]
RP INTERACTION WITH DHX34.
RX PubMed=25220460; DOI=10.1016/j.celrep.2014.08.020;
RA Hug N., Caceres J.F.;
RT "The RNA helicase DHX34 activates NMD by promoting a transition from the
RT surveillance to the decay-inducing complex.";
RL Cell Rep. 8:1845-1856(2014).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 1239-1419, FUNCTION, COFACTOR,
RP CATALYTIC ACTIVITY, AND MUTAGENESIS OF ASP-1353.
RX PubMed=17053788; DOI=10.1038/sj.emboj.7601377;
RA Glavan F., Behm-Ansmant I., Izaurralde E., Conti E.;
RT "Structures of the PIN domains of SMG6 and SMG5 reveal a nuclease within
RT the mRNA surveillance complex.";
RL EMBO J. 25:5117-5125(2006).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1239-1419.
RX PubMed=17557331; DOI=10.1002/prot.21351;
RA Takeshita D., Zenno S., Lee W.C., Saigo K., Tanokura M.;
RT "Crystal structure of the PIN domain of human telomerase-associated protein
RT EST1A.";
RL Proteins 68:980-989(2007).
CC -!- FUNCTION: Component of the telomerase ribonucleoprotein (RNP) complex
CC that is essential for the replication of chromosome termini
CC (PubMed:19179534). May have a general role in telomere regulation
CC (PubMed:12676087, PubMed:12699629). Promotes in vitro the ability of
CC TERT to elongate telomeres (PubMed:12676087, PubMed:12699629).
CC Overexpression induces telomere uncapping, chromosomal end-to-end
CC fusions (telomeric DNA persists at the fusion points) and did not
CC perturb TRF2 telomeric localization (PubMed:12676087, PubMed:12699629).
CC Binds to the single-stranded 5'-(GTGTGG)(4)GTGT-3' telomeric DNA, but
CC not to a telomerase RNA template component (TER) (PubMed:12676087,
CC PubMed:12699629). {ECO:0000269|PubMed:12676087,
CC ECO:0000269|PubMed:12699629, ECO:0000269|PubMed:19179534}.
CC -!- FUNCTION: Plays a role in nonsense-mediated mRNA decay
CC (PubMed:18974281, PubMed:19060897, PubMed:20930030, PubMed:17053788).
CC Is thought to provide a link to the mRNA degradation machinery as it
CC has endonuclease activity required to initiate NMD, and to serve as an
CC adapter for UPF1 to protein phosphatase 2A (PP2A), thereby triggering
CC UPF1 dephosphorylation (PubMed:18974281, PubMed:19060897,
CC PubMed:20930030, PubMed:17053788). Degrades single-stranded RNA
CC (ssRNA), but not ssDNA or dsRNA (PubMed:18974281, PubMed:19060897,
CC PubMed:20930030, PubMed:17053788). {ECO:0000269|PubMed:17053788,
CC ECO:0000269|PubMed:18974281, ECO:0000269|PubMed:19060897,
CC ECO:0000269|PubMed:20930030}.
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:17053788};
CC -!- SUBUNIT: May form homooligomers (PubMed:20930030). Associated component
CC of the telomerase holoenzyme complex (PubMed:19179534). Interacts with
CC TERT, independently of the telomerase RNA (PubMed:12676087,
CC PubMed:12699629). Interacts with SMG1, SMG5, SMG7, UPF1, UPF2, UPF3B
CC and the PP2A catalytic subunits (PubMed:12554878, PubMed:19060897,
CC PubMed:20930030). Also interacts with the exon junction complex (EJC)
CC composed at least of CASC3, EIF4A3, MAGOH and RBM8A; required for the
CC process of nonsense-mediated mRNA decay (PubMed:20930030). Interacts
CC with DHX34; the interaction is RNA-independent (PubMed:25220460).
CC {ECO:0000269|PubMed:12554878, ECO:0000269|PubMed:12676087,
CC ECO:0000269|PubMed:12699629, ECO:0000269|PubMed:19060897,
CC ECO:0000269|PubMed:19179534, ECO:0000269|PubMed:20930030,
CC ECO:0000269|PubMed:25220460}.
CC -!- INTERACTION:
CC Q86US8; P55212: CASP6; NbExp=3; IntAct=EBI-3232100, EBI-718729;
CC Q86US8; O00291: HIP1; NbExp=3; IntAct=EBI-3232100, EBI-473886;
CC Q86US8; P13473-2: LAMP2; NbExp=3; IntAct=EBI-3232100, EBI-21591415;
CC Q86US8; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-3232100, EBI-16439278;
CC Q86US8; O75400-2: PRPF40A; NbExp=3; IntAct=EBI-3232100, EBI-5280197;
CC Q86US8; P62826: RAN; NbExp=3; IntAct=EBI-3232100, EBI-286642;
CC Q86US8; Q92900-2: UPF1; NbExp=2; IntAct=EBI-3232100, EBI-373492;
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:12676087}.
CC Chromosome, telomere {ECO:0000305|PubMed:12699629}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:12676087}. Note=Particularly enriched in the
CC nucleolus. {ECO:0000269|PubMed:12676087}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q86US8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q86US8-2; Sequence=VSP_010360, VSP_010361;
CC Name=3;
CC IsoId=Q86US8-3; Sequence=VSP_047157;
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:12676087,
CC ECO:0000269|PubMed:12699629}.
CC -!- DOMAIN: The PINc domain confers endonuclease activity and is expected
CC to bind the catalytic metal ion. {ECO:0000269|PubMed:18974281,
CC ECO:0000269|PubMed:19060897}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH64916.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA34452.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY145883; AAN46114.1; -; mRNA.
DR EMBL; AB018275; BAA34452.2; ALT_INIT; mRNA.
DR EMBL; AL133597; CAB63733.1; -; mRNA.
DR EMBL; AY168921; AAO17581.1; -; mRNA.
DR EMBL; AK302964; BAH13860.1; -; mRNA.
DR EMBL; AC090617; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL450226; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471108; EAW90559.1; -; Genomic_DNA.
DR EMBL; BC064916; AAH64916.1; ALT_INIT; mRNA.
DR CCDS; CCDS11016.1; -. [Q86US8-1]
DR CCDS; CCDS58498.1; -. [Q86US8-3]
DR PIR; T43475; T43475.
DR RefSeq; NP_001243756.1; NM_001256827.1. [Q86US8-3]
DR RefSeq; NP_001243757.1; NM_001256828.1. [Q86US8-3]
DR RefSeq; NP_001269255.1; NM_001282326.1. [Q86US8-2]
DR RefSeq; NP_060045.4; NM_017575.4. [Q86US8-1]
DR RefSeq; XP_005256626.1; XM_005256569.3.
DR RefSeq; XP_005256628.1; XM_005256571.4. [Q86US8-3]
DR RefSeq; XP_011522071.1; XM_011523769.2.
DR RefSeq; XP_011522077.1; XM_011523775.2. [Q86US8-3]
DR RefSeq; XP_016879888.1; XM_017024399.1. [Q86US8-3]
DR PDB; 2DOK; X-ray; 1.80 A; A/B=1239-1419.
DR PDB; 2HWW; X-ray; 1.80 A; A/B/C=1239-1419.
DR PDB; 2HWX; X-ray; 1.90 A; A=1239-1419.
DR PDB; 4UM2; X-ray; 2.10 A; A=580-1166.
DR PDBsum; 2DOK; -.
DR PDBsum; 2HWW; -.
DR PDBsum; 2HWX; -.
DR PDBsum; 4UM2; -.
DR AlphaFoldDB; Q86US8; -.
DR SMR; Q86US8; -.
DR BioGRID; 116888; 75.
DR CORUM; Q86US8; -.
DR IntAct; Q86US8; 22.
DR MINT; Q86US8; -.
DR STRING; 9606.ENSP00000263073; -.
DR DrugBank; DB05036; Grn163l.
DR iPTMnet; Q86US8; -.
DR MetOSite; Q86US8; -.
DR PhosphoSitePlus; Q86US8; -.
DR BioMuta; SMG6; -.
DR DMDM; 91771922; -.
DR EPD; Q86US8; -.
DR jPOST; Q86US8; -.
DR MassIVE; Q86US8; -.
DR MaxQB; Q86US8; -.
DR PaxDb; Q86US8; -.
DR PeptideAtlas; Q86US8; -.
DR PRIDE; Q86US8; -.
DR ProteomicsDB; 6930; -.
DR ProteomicsDB; 69880; -. [Q86US8-1]
DR ProteomicsDB; 69881; -. [Q86US8-2]
DR Antibodypedia; 50527; 75 antibodies from 13 providers.
DR DNASU; 23293; -.
DR Ensembl; ENST00000263073.11; ENSP00000263073.5; ENSG00000070366.14. [Q86US8-1]
DR Ensembl; ENST00000354901.8; ENSP00000346977.4; ENSG00000070366.14. [Q86US8-3]
DR Ensembl; ENST00000536871.6; ENSP00000440283.2; ENSG00000070366.14. [Q86US8-3]
DR GeneID; 23293; -.
DR KEGG; hsa:23293; -.
DR MANE-Select; ENST00000263073.11; ENSP00000263073.5; NM_017575.5; NP_060045.4.
DR UCSC; uc002fub.2; human. [Q86US8-1]
DR CTD; 23293; -.
DR DisGeNET; 23293; -.
DR GeneCards; SMG6; -.
DR HGNC; HGNC:17809; SMG6.
DR HPA; ENSG00000070366; Low tissue specificity.
DR MIM; 610963; gene.
DR neXtProt; NX_Q86US8; -.
DR OpenTargets; ENSG00000070366; -.
DR PharmGKB; PA25584; -.
DR VEuPathDB; HostDB:ENSG00000070366; -.
DR eggNOG; KOG2162; Eukaryota.
DR GeneTree; ENSGT00940000155300; -.
DR HOGENOM; CLU_004735_0_0_1; -.
DR InParanoid; Q86US8; -.
DR OMA; KDFMPPQ; -.
DR OrthoDB; 556396at2759; -.
DR PhylomeDB; Q86US8; -.
DR TreeFam; TF327119; -.
DR PathwayCommons; Q86US8; -.
DR Reactome; R-HSA-975957; Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC).
DR SignaLink; Q86US8; -.
DR BioGRID-ORCS; 23293; 653 hits in 1090 CRISPR screens.
DR ChiTaRS; SMG6; human.
DR EvolutionaryTrace; Q86US8; -.
DR GeneWiki; SMG6; -.
DR GenomeRNAi; 23293; -.
DR Pharos; Q86US8; Tbio.
DR PRO; PR:Q86US8; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q86US8; protein.
DR Bgee; ENSG00000070366; Expressed in stromal cell of endometrium and 123 other tissues.
DR ExpressionAtlas; Q86US8; baseline and differential.
DR Genevisible; Q86US8; HS.
DR GO; GO:0000781; C:chromosome, telomeric region; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:HGNC-UCL.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:BHF-UCL.
DR GO; GO:0005634; C:nucleus; IDA:HGNC-UCL.
DR GO; GO:0005697; C:telomerase holoenzyme complex; IBA:GO_Central.
DR GO; GO:0070182; F:DNA polymerase binding; IPI:BHF-UCL.
DR GO; GO:0004521; F:endoribonuclease activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0043021; F:ribonucleoprotein complex binding; IPI:BHF-UCL.
DR GO; GO:0003723; F:RNA binding; IPI:BHF-UCL.
DR GO; GO:0070034; F:telomerase RNA binding; IPI:BHF-UCL.
DR GO; GO:0042162; F:telomeric DNA binding; IDA:HGNC-UCL.
DR GO; GO:0006406; P:mRNA export from nucleus; TAS:HGNC-UCL.
DR GO; GO:1904354; P:negative regulation of telomere capping; IDA:BHF-UCL.
DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; IMP:UniProtKB.
DR GO; GO:0035303; P:regulation of dephosphorylation; TAS:HGNC-UCL.
DR GO; GO:0051972; P:regulation of telomerase activity; IC:BHF-UCL.
DR GO; GO:0032204; P:regulation of telomere maintenance; IMP:BHF-UCL.
DR GO; GO:0032210; P:regulation of telomere maintenance via telomerase; TAS:BHF-UCL.
DR Gene3D; 1.25.40.10; -; 1.
DR InterPro; IPR018834; DNA/RNA-bd_Est1-type.
DR InterPro; IPR045153; Est1/Ebs1-like.
DR InterPro; IPR019458; Est1_N.
DR InterPro; IPR029060; PIN-like_dom_sf.
DR InterPro; IPR002716; PIN_dom.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR PANTHER; PTHR15696; PTHR15696; 1.
DR Pfam; PF10374; EST1; 1.
DR Pfam; PF10373; EST1_DNA_bind; 1.
DR Pfam; PF13638; PIN_4; 1.
DR SMART; SM00670; PINc; 1.
DR SUPFAM; SSF48452; SSF48452; 1.
DR SUPFAM; SSF88723; SSF88723; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chromosome; Coiled coil; Cytoplasm;
KW DNA-binding; Endonuclease; Hydrolase; Manganese; Metal-binding;
KW Methylation; Nonsense-mediated mRNA decay; Nuclease; Nucleus;
KW Phosphoprotein; Reference proteome; Telomere.
FT CHAIN 1..1419
FT /note="Telomerase-binding protein EST1A"
FT /id="PRO_0000087069"
FT DOMAIN 1246..1397
FT /note="PINc"
FT REGION 25..79
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 39..59
FT /note="EJC-binding motif 1; mediates interaction with the
FT EJC"
FT REGION 99..165
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 114..503
FT /note="Interaction with telomeric DNA"
FT REGION 133..153
FT /note="EJC-binding motif 2; mediates interaction with the
FT EJC"
FT REGION 177..405
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 419..472
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 854..883
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 163..193
FT /evidence="ECO:0000255"
FT COILED 567..625
FT /evidence="ECO:0000255"
FT COILED 1197..1239
FT /evidence="ECO:0000255"
FT COMPBIAS 30..79
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 99..125
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 129..144
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 177..203
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 212..245
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 257..272
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 275..345
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 364..402
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 861..883
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 1251
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305"
FT BINDING 1353
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305"
FT BINDING 1392
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305"
FT MOD_RES 203
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 332
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P61406"
FT MOD_RES 406
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:P61406"
FT MOD_RES 433
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:P61406"
FT MOD_RES 471
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P61406"
FT MOD_RES 479
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 484
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 831
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 870
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 874
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..1089
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_010360"
FT VAR_SEQ 1..908
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_047157"
FT VAR_SEQ 1090..1119
FT /note="ILEEDRLLSGFVPLLAAPQDPCYVEKTSDK -> MRFRLCHQRGCCPHEREN
FT TCTCKMIISSLQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_010361"
FT VARIANT 291
FT /note="R -> P (in dbSNP:rs1885986)"
FT /evidence="ECO:0000269|PubMed:9872452"
FT /id="VAR_018499"
FT VARIANT 294
FT /note="K -> Q (in dbSNP:rs216195)"
FT /id="VAR_018500"
FT VARIANT 341
FT /note="N -> T (in dbSNP:rs1885987)"
FT /evidence="ECO:0000269|PubMed:12676087,
FT ECO:0000269|PubMed:9872452"
FT /id="VAR_018501"
FT VARIANT 575
FT /note="N -> S (in dbSNP:rs34047637)"
FT /id="VAR_050978"
FT VARIANT 972
FT /note="A -> T (in dbSNP:rs903160)"
FT /id="VAR_018502"
FT VARIANT 984
FT /note="R -> C (in dbSNP:rs35173108)"
FT /id="VAR_050979"
FT VARIANT 1189
FT /note="E -> K (in dbSNP:rs58801957)"
FT /id="VAR_061648"
FT VARIANT 1233
FT /note="H -> R (in dbSNP:rs2273980)"
FT /id="VAR_018503"
FT MUTAGEN 46..52
FT /note="RPDLEIY->EPDLEIE: Alters interaction with the EJC.
FT Loss of interaction with the EJC; when associated with 140-
FT E--E-146."
FT /evidence="ECO:0000269|PubMed:20930030"
FT MUTAGEN 140..146
FT /note="KPDLQIY->EPDLQIE: Alters interaction with the EJC.
FT Loss of interaction with the EJC; when associated with 46-
FT E--E-52."
FT /evidence="ECO:0000269|PubMed:20930030"
FT MUTAGEN 1251
FT /note="D->A: Impaired nonsense-mediated RNA decay."
FT /evidence="ECO:0000269|PubMed:18974281,
FT ECO:0000269|PubMed:19060897"
FT MUTAGEN 1251
FT /note="D->N: Loss of endonuclease activity and nonsense-
FT mediated RNA decay; when associated with N-1392."
FT /evidence="ECO:0000269|PubMed:18974281,
FT ECO:0000269|PubMed:19060897"
FT MUTAGEN 1353
FT /note="D->A: Abolishes RNase activity."
FT /evidence="ECO:0000269|PubMed:17053788,
FT ECO:0000269|PubMed:19060897"
FT MUTAGEN 1392
FT /note="D->A: Impaired nonsense-mediated RNA decay; when
FT associated with A-1251."
FT /evidence="ECO:0000269|PubMed:18974281,
FT ECO:0000269|PubMed:19060897"
FT MUTAGEN 1392
FT /note="D->N: Loss of endonuclease activity and nonsense-
FT mediated RNA decay; when associated with N-1251."
FT /evidence="ECO:0000269|PubMed:18974281,
FT ECO:0000269|PubMed:19060897"
FT HELIX 580..600
FT /evidence="ECO:0007829|PDB:4UM2"
FT STRAND 601..603
FT /evidence="ECO:0007829|PDB:4UM2"
FT HELIX 606..629
FT /evidence="ECO:0007829|PDB:4UM2"
FT HELIX 631..636
FT /evidence="ECO:0007829|PDB:4UM2"
FT HELIX 639..647
FT /evidence="ECO:0007829|PDB:4UM2"
FT HELIX 649..660
FT /evidence="ECO:0007829|PDB:4UM2"
FT HELIX 667..696
FT /evidence="ECO:0007829|PDB:4UM2"
FT HELIX 700..703
FT /evidence="ECO:0007829|PDB:4UM2"
FT HELIX 716..742
FT /evidence="ECO:0007829|PDB:4UM2"
FT HELIX 749..761
FT /evidence="ECO:0007829|PDB:4UM2"
FT HELIX 767..778
FT /evidence="ECO:0007829|PDB:4UM2"
FT HELIX 782..793
FT /evidence="ECO:0007829|PDB:4UM2"
FT STRAND 795..797
FT /evidence="ECO:0007829|PDB:4UM2"
FT HELIX 801..820
FT /evidence="ECO:0007829|PDB:4UM2"
FT HELIX 880..882
FT /evidence="ECO:0007829|PDB:4UM2"
FT HELIX 885..905
FT /evidence="ECO:0007829|PDB:4UM2"
FT HELIX 909..911
FT /evidence="ECO:0007829|PDB:4UM2"
FT HELIX 912..928
FT /evidence="ECO:0007829|PDB:4UM2"
FT STRAND 929..931
FT /evidence="ECO:0007829|PDB:4UM2"
FT HELIX 936..951
FT /evidence="ECO:0007829|PDB:4UM2"
FT HELIX 966..992
FT /evidence="ECO:0007829|PDB:4UM2"
FT HELIX 1001..1003
FT /evidence="ECO:0007829|PDB:4UM2"
FT HELIX 1006..1008
FT /evidence="ECO:0007829|PDB:4UM2"
FT HELIX 1012..1014
FT /evidence="ECO:0007829|PDB:4UM2"
FT HELIX 1017..1020
FT /evidence="ECO:0007829|PDB:4UM2"
FT HELIX 1023..1035
FT /evidence="ECO:0007829|PDB:4UM2"
FT HELIX 1037..1039
FT /evidence="ECO:0007829|PDB:4UM2"
FT HELIX 1057..1068
FT /evidence="ECO:0007829|PDB:4UM2"
FT STRAND 1079..1081
FT /evidence="ECO:0007829|PDB:4UM2"
FT STRAND 1086..1088
FT /evidence="ECO:0007829|PDB:4UM2"
FT HELIX 1092..1097
FT /evidence="ECO:0007829|PDB:4UM2"
FT HELIX 1101..1105
FT /evidence="ECO:0007829|PDB:4UM2"
FT STRAND 1112..1114
FT /evidence="ECO:0007829|PDB:4UM2"
FT HELIX 1119..1139
FT /evidence="ECO:0007829|PDB:4UM2"
FT STRAND 1140..1143
FT /evidence="ECO:0007829|PDB:4UM2"
FT STRAND 1145..1149
FT /evidence="ECO:0007829|PDB:4UM2"
FT STRAND 1152..1155
FT /evidence="ECO:0007829|PDB:4UM2"
FT STRAND 1240..1250
FT /evidence="ECO:0007829|PDB:2DOK"
FT HELIX 1252..1268
FT /evidence="ECO:0007829|PDB:2DOK"
FT STRAND 1270..1276
FT /evidence="ECO:0007829|PDB:2DOK"
FT HELIX 1277..1287
FT /evidence="ECO:0007829|PDB:2DOK"
FT HELIX 1298..1319
FT /evidence="ECO:0007829|PDB:2DOK"
FT STRAND 1325..1328
FT /evidence="ECO:0007829|PDB:2DOK"
FT STRAND 1334..1336
FT /evidence="ECO:0007829|PDB:2DOK"
FT HELIX 1352..1361
FT /evidence="ECO:0007829|PDB:2DOK"
FT HELIX 1368..1371
FT /evidence="ECO:0007829|PDB:2DOK"
FT STRAND 1381..1389
FT /evidence="ECO:0007829|PDB:2DOK"
FT HELIX 1393..1401
FT /evidence="ECO:0007829|PDB:2DOK"
FT HELIX 1409..1416
FT /evidence="ECO:0007829|PDB:2DOK"
SQ SEQUENCE 1419 AA; 160462 MW; 93FC7DDA68BD218C CRC64;
MAEGLERVRI SASELRGILA TLAPQAGSRE NMKELKEARP RKDNRRPDLE IYKPGLSRLR
NKPKIKEPPG SEEFKDEIVN DRDCSAVENG TQPVKDVCKE LNNQEQNGPI DPENNRGQES
FPRTAGQEDR SLKIIKRTKK PDLQIYQPGR RLQTVSKESA SRVEEEEVLN QVEQLRVEED
ECRGNVAKEE VANKPDRAEI EKSPGGGRVG AAKGEKGKRM GKGEGVRETH DDPARGRPGS
AKRYSRSDKR RNRYRTRSTS SAGSNNSAEG AGLTDNGCRR RRQDRTKERP RLKKQVSVSS
TDSLDEDRID EPDGLGPRRS SERKRHLERN WSGRGEGEQK NSAKEYRGTL RVTFDAEAMN
KESPMVRSAR DDMDRGKPDK GLSSGGKGSE KQESKNPKQE LRGRGRGILI LPAHTTLSVN
SAGSPESAPL GPRLLFGSGS KGSRSWGRGG TTRRLWDPNN PDQKPALKTQ TPQLHFLDTD
DEVSPTSWGD SRQAQASYYK FQNSDNPYYY PRTPGPASQY PYTGYNPLQY PVGPTNGVYP
GPYYPGYPTP SGQYVCSPLP TSTMSPEEVE QHMRNLQQQE LHRLLRVADN QELQLSNLLS
RDRISPEGLE KMAQLRAELL QLYERCILLD IEFSDNQNVD QILWKNAFYQ VIEKFRQLVK
DPNVENPEQI RNRLLELLDE GSDFFDSLLQ KLQVTYKFKL EDYMDGLAIR SKPLRKTVKY
ALISAQRCMI CQGDIARYRE QASDTANYGK ARSWYLKAQH IAPKNGRPYN QLALLAVYTR
RKLDAVYYYM RSLAASNPIL TAKESLMSLF EETKRKAEQM EKKQHEEFDL SPDQWRKGKK
STFRHVGDDT TRLEIWIHPS HPRSSQGTES GKDSEQENGL GSLSPSDLNK RFILSFLHAH
GKLFTRIGME TFPAVAEKVL KEFQVLLQHS PSPIGSTRML QLMTINMFAV HNSQLKDCFS
EECRSVIQEQ AAALGLAMFS LLVRRCTCLL KESAKAQLSS PEDQDDQDDI KVSSFVPDLK
ELLPSVKVWS DWMLGYPDTW NPPPTSLDLP SHVAVDVWST LADFCNILTA VNQSEVPLYK
DPDDDLTLLI LEEDRLLSGF VPLLAAPQDP CYVEKTSDKV IAADCKRVTV LKYFLEALCG
QEEPLLAFKG GKYVSVAPVP DTMGKEMGSQ EGTRLEDEEE DVVIEDFEED SEAEGSGGED
DIRELRAKKL ALARKIAEQQ RRQEKIQAVL EDHSQMRQME LEIRPLFLVP DTNGFIDHLA
SLARLLESRK YILVVPLIVI NELDGLAKGQ ETDHRAGGYA RVVQEKARKS IEFLEQRFES
RDSCLRALTS RGNELESIAF RSEDITGQLG NNDDLILSCC LHYCKDKAKD FMPASKEEPI
RLLREVVLLT DDRNLRVKAL TRNVPVRDIP AFLTWAQVG
