TGS1_YEAST
ID TGS1_YEAST Reviewed; 315 AA.
AC Q12052; D6W3L1;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Trimethylguanosine synthase;
DE EC=2.1.1.- {ECO:0000269|PubMed:18775984};
DE AltName: Full=Cap-specific guanine-N2 methyltransferase;
DE AltName: Full=snRNA/snoRNA cap hypermethylase;
GN Name=TGS1; OrderedLocusNames=YPL157W; ORFNames=P2573;
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 [GENOMIC DNA].
RC STRAIN=ATCC 204511 / S288c / AB972;
RX PubMed=8948103;
RX DOI=10.1002/(sici)1097-0061(199611)12:14<1483::aid-yea34>3.0.co;2-o;
RA Purnelle B., Coster F., Goffeau A.;
RT "The sequence of 55 kb on the left arm of yeast chromosome XVI identifies a
RT small nuclear RNA, a new putative protein kinase and two new putative
RT regulators.";
RL Yeast 12:1483-1492(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169875;
RA Bussey H., Storms R.K., Ahmed A., Albermann K., Allen E., Ansorge W.,
RA Araujo R., Aparicio A., Barrell B.G., Badcock K., Benes V., Botstein D.,
RA Bowman S., Brueckner M., Carpenter J., Cherry J.M., Chung E.,
RA Churcher C.M., Coster F., Davis K., Davis R.W., Dietrich F.S., Delius H.,
RA DiPaolo T., Dubois E., Duesterhoeft A., Duncan M., Floeth M., Fortin N.,
RA Friesen J.D., Fritz C., Goffeau A., Hall J., Hebling U., Heumann K.,
RA Hilbert H., Hillier L.W., Hunicke-Smith S., Hyman R.W., Johnston M.,
RA Kalman S., Kleine K., Komp C., Kurdi O., Lashkari D., Lew H., Lin A.,
RA Lin D., Louis E.J., Marathe R., Messenguy F., Mewes H.-W., Mirtipati S.,
RA Moestl D., Mueller-Auer S., Namath A., Nentwich U., Oefner P., Pearson D.,
RA Petel F.X., Pohl T.M., Purnelle B., Rajandream M.A., Rechmann S.,
RA Rieger M., Riles L., Roberts D., Schaefer M., Scharfe M., Scherens B.,
RA Schramm S., Schroeder M., Sdicu A.-M., Tettelin H., Urrestarazu L.A.,
RA Ushinsky S., Vierendeels F., Vissers S., Voss H., Walsh S.V., Wambutt R.,
RA Wang Y., Wedler E., Wedler H., Winnett E., Zhong W.-W., Zollner A.,
RA Vo D.H., Hani J.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XVI.";
RL Nature 387:103-105(1997).
RN [3]
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 [4]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CBF5; NOP58 AND SMB1, AND
RP MUTAGENESIS OF ASP-103 AND ASP-126.
RX PubMed=11983179; DOI=10.1016/s1097-2765(02)00484-7;
RA Mouaikel J., Verheggen C., Bertrand E., Tazi J., Bordonne R.;
RT "Hypermethylation of the cap structure of both yeast snRNAs and snoRNAs
RT requires a conserved methyltransferase that is localized to the
RT nucleolus.";
RL Mol. Cell 9:891-901(2002).
RN [5]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [6]
RP FUNCTION, AND MUTAGENESIS OF TRP-75; GLU-81; ILE-83; SER-175 AND TRP-178.
RX PubMed=12907733; DOI=10.1093/nar/gkg656;
RA Mouaikel J., Bujnicki J.M., Tazi J., Bordonne R.;
RT "Sequence-structure-function relationships of Tgs1, the yeast snRNA/snoRNA
RT cap hypermethylase.";
RL Nucleic Acids Res. 31:4899-4909(2003).
RN [7]
RP FUNCTION, AND MUTAGENESIS OF ASP-103 AND TRP-178.
RX PubMed=15340060; DOI=10.1128/mcb.24.18.7976-7986.2004;
RA Colau G., Thiry M., Leduc V., Bordonne R., Lafontaine D.L.J.;
RT "The small nucle(ol)ar RNA cap trimethyltransferase is required for
RT ribosome synthesis and intact nucleolar morphology.";
RL Mol. Cell. Biol. 24:7976-7986(2004).
RN [8]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=18775984; DOI=10.1074/jbc.m806127200;
RA Hausmann S., Zheng S., Costanzo M., Brost R.L., Garcin D., Boone C.,
RA Shuman S., Schwer B.;
RT "Genetic and biochemical analysis of yeast and human cap trimethylguanosine
RT synthase: functional overlap of 2,2,7-trimethylguanosine caps, small
RT nuclear ribonucleoprotein components, pre-mRNA splicing factors, and RNA
RT decay pathways.";
RL J. Biol. Chem. 283:31706-31718(2008).
RN [9]
RP FUNCTION, AND MUTAGENESIS OF TRP-178.
RX PubMed=18840651; DOI=10.1242/jcs.033308;
RA Franke J., Gehlen J., Ehrenhofer-Murray A.E.;
RT "Hypermethylation of yeast telomerase RNA by the snRNA and snoRNA
RT methyltransferase Tgs1.";
RL J. Cell Sci. 121:3553-3560(2008).
CC -!- FUNCTION: Catalyzes the two serial methylation steps for the conversion
CC of the 7-monomethylguanosine (m(7)G) caps of snRNAs and snoRNAs to a
CC 2,2,7-trimethylguanosine (m(2,2,7)G) cap structure. The enzyme is
CC specific for guanine, and N7 methylation must precede N2 methylation.
CC Hypermethylates the m3G cap on TLC1 telomerase which affects telomere
CC silencing and telomere length regulation. Required for pre-mRNA
CC splicing, pre-rRNA processing and small ribosomal subunit synthesis.
CC Involved in nucleolar structural organization.
CC {ECO:0000269|PubMed:11983179, ECO:0000269|PubMed:12907733,
CC ECO:0000269|PubMed:15340060, ECO:0000269|PubMed:18775984,
CC ECO:0000269|PubMed:18840651}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside
CC in mRNA + S-adenosyl-L-methionine = a 5'-end (N(2),N(7)-dimethyl 5'-
CC triphosphoguanosine)-ribonucleoside in mRNA + H(+) + S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:67620, Rhea:RHEA-COMP:17167, Rhea:RHEA-
CC COMP:17315, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:156461, ChEBI:CHEBI:172880;
CC Evidence={ECO:0000269|PubMed:18775984};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67621;
CC Evidence={ECO:0000269|PubMed:18775984};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end (N(2),N(7)-dimethyl 5'-triphosphoguanosine)-
CC ribonucleoside in mRNA + S-adenosyl-L-methionine = a 5'-end
CC (N(2),N(2),N(7)-trimethyl 5'-triphosphoguanosine)-(ribonucleoside) in
CC mRNA + H(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:67624,
CC Rhea:RHEA-COMP:17171, Rhea:RHEA-COMP:17315, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:167623,
CC ChEBI:CHEBI:172880; Evidence={ECO:0000269|PubMed:18775984};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67625;
CC Evidence={ECO:0000269|PubMed:18775984};
CC -!- ACTIVITY REGULATION: Substrate inhibited by S-adenosyl-L-homocysteine.
CC {ECO:0000250}.
CC -!- SUBUNIT: Monomer (By similarity). Interacts with the spliceosomal snRNP
CC core component SMB1 and the snoRNP components CBF5 and NOP58.
CC {ECO:0000250, ECO:0000269|PubMed:11983179}.
CC -!- INTERACTION:
CC Q12052; P40342: SWM2; NbExp=5; IntAct=EBI-30910, EBI-28438;
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:11983179,
CC ECO:0000269|PubMed:14562095}.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily.
CC Trimethylguanosine synthase family. {ECO:0000305}.
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DR EMBL; X96770; CAA65564.1; -; Genomic_DNA.
DR EMBL; Z73513; CAA97862.1; -; Genomic_DNA.
DR EMBL; BK006949; DAA11277.1; -; Genomic_DNA.
DR PIR; S65168; S65168.
DR RefSeq; NP_015168.1; NM_001183971.1.
DR AlphaFoldDB; Q12052; -.
DR SMR; Q12052; -.
DR BioGRID; 36026; 502.
DR DIP; DIP-1974N; -.
DR IntAct; Q12052; 4.
DR MINT; Q12052; -.
DR STRING; 4932.YPL157W; -.
DR iPTMnet; Q12052; -.
DR MaxQB; Q12052; -.
DR PaxDb; Q12052; -.
DR PRIDE; Q12052; -.
DR EnsemblFungi; YPL157W_mRNA; YPL157W; YPL157W.
DR GeneID; 855946; -.
DR KEGG; sce:YPL157W; -.
DR SGD; S000006078; TGS1.
DR VEuPathDB; FungiDB:YPL157W; -.
DR eggNOG; KOG2730; Eukaryota.
DR GeneTree; ENSGT00390000018056; -.
DR HOGENOM; CLU_029658_2_0_1; -.
DR InParanoid; Q12052; -.
DR OMA; LACAKHN; -.
DR BioCyc; YEAST:G3O-34053-MON; -.
DR BRENDA; 2.3.1.221; 530.
DR PRO; PR:Q12052; -.
DR Proteomes; UP000002311; Chromosome XVI.
DR RNAct; Q12052; protein.
DR GO; GO:0005730; C:nucleolus; IDA:SGD.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0008173; F:RNA methyltransferase activity; IMP:SGD.
DR GO; GO:0071164; F:RNA trimethylguanosine synthase activity; IBA:GO_Central.
DR GO; GO:0036261; P:7-methylguanosine cap hypermethylation; IMP:SGD.
DR GO; GO:0009452; P:7-methylguanosine RNA capping; IEA:InterPro.
DR GO; GO:0051321; P:meiotic cell cycle; IMP:SGD.
DR GO; GO:0017126; P:nucleologenesis; IMP:SGD.
DR GO; GO:0032210; P:regulation of telomere maintenance via telomerase; IMP:SGD.
DR GO; GO:0001510; P:RNA methylation; IMP:SGD.
DR GO; GO:0008033; P:tRNA processing; IMP:SGD.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR019012; RNA_cap_Gua-N2-MeTrfase.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR Pfam; PF09445; Methyltransf_15; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 1: Evidence at protein level;
KW Methyltransferase; Nucleus; Reference proteome; S-adenosyl-L-methionine;
KW Transferase.
FT CHAIN 1..315
FT /note="Trimethylguanosine synthase"
FT /id="PRO_0000270619"
FT REGION 1..58
FT /note="Required for correct nucleolar localization"
FT REGION 271..315
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 273..303
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 126
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000305"
FT MUTAGEN 75
FT /note="W->A: No effect."
FT /evidence="ECO:0000269|PubMed:12907733"
FT MUTAGEN 81
FT /note="E->A: No effect."
FT /evidence="ECO:0000269|PubMed:12907733"
FT MUTAGEN 83
FT /note="I->R: Loss of function."
FT /evidence="ECO:0000269|PubMed:12907733"
FT MUTAGEN 103
FT /note="D->A: Loss of catalytic activity, but not required
FT for pre-rRNA processing."
FT /evidence="ECO:0000269|PubMed:11983179,
FT ECO:0000269|PubMed:15340060"
FT MUTAGEN 126
FT /note="D->A: Loss of function."
FT /evidence="ECO:0000269|PubMed:11983179"
FT MUTAGEN 175
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:12907733"
FT MUTAGEN 175
FT /note="S->E,R: Loss of function."
FT /evidence="ECO:0000269|PubMed:12907733"
FT MUTAGEN 178
FT /note="W->A: Loss of catalytic activity, but not required
FT for pre-rRNA processing."
FT /evidence="ECO:0000269|PubMed:12907733,
FT ECO:0000269|PubMed:15340060, ECO:0000269|PubMed:18840651"
SQ SEQUENCE 315 AA; 36527 MW; A7E0ABBE915D6CD4 CRC64;
MGRTFIHASK IKHAARKRKH HSNFRTLIKL LNNDAYKIES SKPLKNGKLF KYWKNRRRLF
SKIDSASIYM TDELWFSVTP ERIACFLANF VKACMPNAER ILDVFCGGGG NTIQFAMQFP
YVYGVDYSIE HIYCTAKNAQ SYGVDDRIWL KRGSWKKLVS KQKLSKIKYD CVFGSPPWGG
PEYLRNDVYD LEQHLKPMGI TKMLKSFLKL SPNVIMFLPR NSDLNQLSRA TRKVLGPFAK
CKVLYVKENG YMKGIFCMWG ECFFNYEPAS TENSRRESSE KEELSSENEE LSKRKKHEST
TTTKDNTVDI YDVNG
