EST3_YEAST
ID EST3_YEAST Reviewed; 181 AA.
AC Q03096; D6VVS0;
DT 01-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-2002, sequence version 2.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Telomere replication protein EST3;
DE AltName: Full=Ever shorter telomeres protein 3;
GN Name=EST3; OrderedLocusNames=YIL009C-A;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169870;
RA Churcher C.M., Bowman S., Badcock K., Bankier A.T., Brown D.,
RA Chillingworth T., Connor R., Devlin K., Gentles S., Hamlin N., Harris D.E.,
RA Horsnell T., Hunt S., Jagels K., Jones M., Lye G., Moule S., Odell C.,
RA Pearson D., Rajandream M.A., Rice P., Rowley N., Skelton J., Smith V.,
RA Walsh S.V., Whitehead S., Barrell B.G.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome IX.";
RL Nature 387:84-87(1997).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [3]
RP FUNCTION.
RX PubMed=8978029; DOI=10.1093/genetics/144.4.1399;
RA Lendvay T.S., Morris D.K., Sah J., Balasubramanian B., Lundblad V.;
RT "Senescence mutants of Saccharomyces cerevisiae with a defect in telomere
RT replication identify three additional EST genes.";
RL Genetics 144:1399-1412(1996).
RN [4]
RP RIBOSOMAL FRAMESHIFT, AND FUNCTION.
RX PubMed=9382847; DOI=10.1016/s0960-9822(06)00416-7;
RA Morris D.K., Lundblad V.;
RT "Programmed translational frameshifting in a gene required for yeast
RT telomere replication.";
RL Curr. Biol. 7:969-976(1997).
RN [5]
RP FUNCTION.
RX PubMed=9326584; DOI=10.1073/pnas.94.21.11190;
RA Lingner J., Cech T.R., Hughes T.R., Lundblad V.;
RT "Three ever shorter telomere (EST) genes are dispensable for in vitro yeast
RT telomerase activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:11190-11195(1997).
RN [6]
RP FUNCTION.
RX PubMed=10619426; DOI=10.1016/s0092-8674(00)81670-0;
RA Diede S.J., Gottschling D.E.;
RT "Telomerase-mediated telomere addition in vivo requires DNA primase and DNA
RT polymerases alpha and delta.";
RL Cell 99:723-733(1999).
RN [7]
RP COMPONENT OF THE TELOMERASE COMPLEX, AND INTERACTION WITH THE TELOMERASE
RP RNA COMPONENT TLC1.
RX PubMed=10898986; DOI=10.1016/s0960-9822(00)00562-5;
RA Hughes T.R., Evans S.K., Weilbaecher R.G., Lundblad V.;
RT "The Est3 protein is a subunit of yeast telomerase.";
RL Curr. Biol. 10:809-812(2000).
RN [8]
RP FUNCTION, DNA-BINDING, RNA-BINDING, AND MUTAGENESIS OF GLU-104.
RX PubMed=16884717; DOI=10.1016/j.febslet.2006.07.048;
RA Sharanov Y.S., Zvereva M.I., Dontsova O.A.;
RT "Saccharomyces cerevisiae telomerase subunit Est3p binds DNA and RNA and
RT stimulates unwinding of RNA/DNA heteroduplexes.";
RL FEBS Lett. 580:4683-4690(2006).
RN [9]
RP FUNCTION, SUBUNIT, AND MUTAGENESIS OF LYS-3; ASP-49; LYS-68; LYS-71;
RP PHE-72; ALA-82; ASP-86; SER-87; PHE-95; PHE-103; THR-115 AND ASP-166.
RX PubMed=16418502; DOI=10.1093/nar/gkj445;
RA Yang C.-P., Chen Y.-B., Meng F.-L., Zhou J.-Q.;
RT "Saccharomyces cerevisiae Est3p dimerizes in vitro and dimerization
RT contributes to efficient telomere replication in vivo.";
RL Nucleic Acids Res. 34:407-416(2006).
RN [10]
RP SUBUNIT.
RX PubMed=17680761; DOI=10.1134/s0006297907070036;
RA Sharanov Y.S., Smekalova E.M., Zvereva M.I., Dontsova O.A.;
RT "Isolation of active yeast telomerase protein Est3p and investigation of
RT its dimerization in vitro.";
RL Biochemistry (Mosc.) 72:702-706(2007).
RN [11]
RP INTERACTION WITH THE TELOMERASE HOLOENZYME, AND MUTAGENESIS OF TRP-21;
RP LYS-68; LYS-71; GLU-104; ARG-110; GLU-114; THR-115; ASN-117; ASP-164;
RP ASP-166 AND VAL-168.
RX PubMed=19172754; DOI=10.1038/nsmb.1472;
RA Lee J., Mandell E.K., Tucey T.M., Morris D.K., Lundblad V.;
RT "The Est3 protein associates with yeast telomerase through an OB-fold
RT domain.";
RL Nat. Struct. Mol. Biol. 15:990-997(2008).
CC -!- FUNCTION: Component of the telomerase complex involved in telomere
CC replication. Stimulates RNA/DNA heteroduplex unwinding which favors the
CC telomere replication by the telomerase. {ECO:0000269|PubMed:10619426,
CC ECO:0000269|PubMed:16418502, ECO:0000269|PubMed:16884717,
CC ECO:0000269|PubMed:8978029, ECO:0000269|PubMed:9326584,
CC ECO:0000269|PubMed:9382847}.
CC -!- SUBUNIT: Homodimer. Component of the telomerase complex composed of
CC EST1, EST2, EST3 and the RNA component TLC1. Interacts with the
CC telomerase RNA component TLC1 in presence of EST2.
CC {ECO:0000269|PubMed:10898986, ECO:0000269|PubMed:16418502,
CC ECO:0000269|PubMed:17680761, ECO:0000269|PubMed:19172754}.
CC -!- INTERACTION:
CC Q03096; Q06163: EST2; NbExp=3; IntAct=EBI-6691, EBI-3764464;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. Chromosome, telomere
CC {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Ribosomal frameshifting; Named isoforms=2;
CC Name=1;
CC IsoId=Q03096-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q03096-2; Sequence=VSP_035813, VSP_035814;
CC -!- MISCELLANEOUS: [Isoform 1]: Produced by ribosomal frameshifting between
CC codon Leu-92 and Val-93.
CC -!- MISCELLANEOUS: [Isoform 2]: Produced from conventional translation of
CC the YIL009C-A ORF. There is no apparent role for isoform 2 in the cell.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the EST3 family. {ECO:0000305}.
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DR EMBL; Z38113; CAA86240.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BK006942; DAA08536.1; -; Genomic_DNA.
DR PIR; S78572; S78572.
DR RefSeq; NP_012256.1; NM_001184306.2. [Q03096-1]
DR PDB; 2M9V; NMR; -; A=13-181.
DR PDBsum; 2M9V; -.
DR AlphaFoldDB; Q03096; -.
DR BMRB; Q03096; -.
DR SMR; Q03096; -.
DR BioGRID; 34981; 62.
DR ComplexPortal; CPX-3298; Telomerase holoenzyme complex.
DR DIP; DIP-6694N; -.
DR IntAct; Q03096; 2.
DR STRING; 4932.YIL009C-A; -.
DR PaxDb; Q03096; -.
DR EnsemblFungi; YIL009C-A_mRNA; YIL009C-A; YIL009C-A. [Q03096-1]
DR GeneID; 854806; -.
DR KEGG; sce:YIL009C-A; -.
DR SGD; S000006432; EST3.
DR VEuPathDB; FungiDB:YIL009C-A; -.
DR eggNOG; ENOG502S5B8; Eukaryota.
DR HOGENOM; CLU_1489823_0_0_1; -.
DR InParanoid; Q03096; -.
DR OMA; TVNCLFV; -.
DR BioCyc; YEAST:G3O-31458-MON; -.
DR PRO; PR:Q03096; -.
DR Proteomes; UP000002311; Chromosome IX.
DR RNAct; Q03096; protein.
DR GO; GO:0000781; C:chromosome, telomeric region; IMP:UniProtKB.
DR GO; GO:0005829; C:cytosol; HDA:SGD.
DR GO; GO:0005634; C:nucleus; IDA:SGD.
DR GO; GO:0005697; C:telomerase holoenzyme complex; IDA:SGD.
DR GO; GO:0033677; F:DNA/RNA helicase activity; IDA:SGD.
DR GO; GO:0003924; F:GTPase activity; IDA:SGD.
DR GO; GO:0042162; F:telomeric DNA binding; IDA:SGD.
DR GO; GO:0051973; P:positive regulation of telomerase activity; IEA:InterPro.
DR GO; GO:0007004; P:telomere maintenance via telomerase; IDA:SGD.
DR InterPro; IPR019437; TPP1/Est3.
DR Pfam; PF10341; TPP1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Chromosome; Nucleus; Reference proteome;
KW Ribosomal frameshifting; Telomere.
FT CHAIN 1..181
FT /note="Telomere replication protein EST3"
FT /id="PRO_0000021206"
FT VAR_SEQ 93
FT /note="V -> S (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_035813"
FT VAR_SEQ 94..181
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_035814"
FT MUTAGEN 3
FT /note="K->A: Causes telomere shortening."
FT /evidence="ECO:0000269|PubMed:16418502"
FT MUTAGEN 21
FT /note="W->A: Causes telomere shortening."
FT /evidence="ECO:0000269|PubMed:19172754"
FT MUTAGEN 49
FT /note="D->A: Reduces ability to dimerize and causes
FT telomere shortening."
FT /evidence="ECO:0000269|PubMed:16418502"
FT MUTAGEN 68
FT /note="K->A: Reduces ability to dimerize and causes
FT telomere shortening."
FT /evidence="ECO:0000269|PubMed:16418502,
FT ECO:0000269|PubMed:19172754"
FT MUTAGEN 68
FT /note="K->E,S,Y: Causes telomere shortening."
FT /evidence="ECO:0000269|PubMed:16418502,
FT ECO:0000269|PubMed:19172754"
FT MUTAGEN 71
FT /note="K->A,E: Causes telomere shortening, but does not
FT impair interaction with the telomerase RNP."
FT /evidence="ECO:0000269|PubMed:16418502,
FT ECO:0000269|PubMed:19172754"
FT MUTAGEN 72
FT /note="F->A: Causes telomere shortening."
FT /evidence="ECO:0000269|PubMed:16418502"
FT MUTAGEN 82
FT /note="A->E: Causes telomere shortening."
FT /evidence="ECO:0000269|PubMed:16418502"
FT MUTAGEN 86
FT /note="D->A: Causes progressive telomere shortening and
FT cell senescence."
FT /evidence="ECO:0000269|PubMed:16418502"
FT MUTAGEN 87
FT /note="S->A: Causes telomere shortening."
FT /evidence="ECO:0000269|PubMed:16418502"
FT MUTAGEN 95
FT /note="F->A: Causes telomere shortening."
FT /evidence="ECO:0000269|PubMed:16418502"
FT MUTAGEN 103
FT /note="F->A: Causes telomere shortening."
FT /evidence="ECO:0000269|PubMed:16418502"
FT MUTAGEN 104
FT /note="E->A: Reduces binding to DNA and RNA, and causes
FT progressive telomere shortening and cell senescence."
FT /evidence="ECO:0000269|PubMed:16884717,
FT ECO:0000269|PubMed:19172754"
FT MUTAGEN 104
FT /note="E->R: Impairs interaction with the telomerase RNP
FT and causes progressive telomere shortening and cell
FT senescence."
FT /evidence="ECO:0000269|PubMed:16884717,
FT ECO:0000269|PubMed:19172754"
FT MUTAGEN 110
FT /note="R->A,E: Causes progressive telomere shortening and
FT cell senescence, but does not impair interaction with the
FT telomerase RNP."
FT /evidence="ECO:0000269|PubMed:19172754"
FT MUTAGEN 114
FT /note="E->A,K: Impairs interaction with the telomerase RNP
FT and causes telomere shortening."
FT /evidence="ECO:0000269|PubMed:19172754"
FT MUTAGEN 115
FT /note="T->A: Impairs interaction with the telomerase RNP
FT and causes telomere shortening."
FT /evidence="ECO:0000269|PubMed:16418502,
FT ECO:0000269|PubMed:19172754"
FT MUTAGEN 117
FT /note="N->A,K: Impairs interaction with the telomerase RNP
FT and causes telomere shortening."
FT /evidence="ECO:0000269|PubMed:19172754"
FT MUTAGEN 164
FT /note="D->A,R: Causes telomere shortening, but does not
FT impair interaction with the telomerase RNP."
FT /evidence="ECO:0000269|PubMed:19172754"
FT MUTAGEN 166
FT /note="D->A: Reduces ability to dimerize and causes
FT telomere shortening."
FT /evidence="ECO:0000269|PubMed:16418502,
FT ECO:0000269|PubMed:19172754"
FT MUTAGEN 166
FT /note="D->R: Impairs interaction with the telomerase RNP
FT and causes telomere shortening."
FT /evidence="ECO:0000269|PubMed:16418502,
FT ECO:0000269|PubMed:19172754"
FT MUTAGEN 168
FT /note="V->A,D,Y: Causes telomere shortening."
FT /evidence="ECO:0000269|PubMed:19172754"
FT HELIX 15..17
FT /evidence="ECO:0007829|PDB:2M9V"
FT HELIX 22..28
FT /evidence="ECO:0007829|PDB:2M9V"
FT TURN 32..34
FT /evidence="ECO:0007829|PDB:2M9V"
FT HELIX 47..51
FT /evidence="ECO:0007829|PDB:2M9V"
FT HELIX 53..55
FT /evidence="ECO:0007829|PDB:2M9V"
FT HELIX 57..60
FT /evidence="ECO:0007829|PDB:2M9V"
FT HELIX 63..65
FT /evidence="ECO:0007829|PDB:2M9V"
FT STRAND 66..76
FT /evidence="ECO:0007829|PDB:2M9V"
FT STRAND 79..85
FT /evidence="ECO:0007829|PDB:2M9V"
FT STRAND 90..95
FT /evidence="ECO:0007829|PDB:2M9V"
FT HELIX 97..107
FT /evidence="ECO:0007829|PDB:2M9V"
FT STRAND 118..124
FT /evidence="ECO:0007829|PDB:2M9V"
FT STRAND 126..131
FT /evidence="ECO:0007829|PDB:2M9V"
FT HELIX 132..137
FT /evidence="ECO:0007829|PDB:2M9V"
FT HELIX 143..145
FT /evidence="ECO:0007829|PDB:2M9V"
FT STRAND 148..164
FT /evidence="ECO:0007829|PDB:2M9V"
FT TURN 177..179
FT /evidence="ECO:0007829|PDB:2M9V"
SQ SEQUENCE 181 AA; 20555 MW; 18AF3DCEEE65DB84 CRC64;
MPKVILESHS KPTDSVFLQP WIKALIEDNS EHDQYHPSGH VIPSLTKQDL ALPHMSPTIL
TNPCHFAKIT KFYNVCDYKV YASIRDSSHQ ILVEFSQECV SNFERTHNCR ITSETTNCLM
IIGDADLVYV TNSRAMSHFK ICLSNISSKE IVPVLNVNQA TIFDIDQVGS LSTFPFVYKY
L
