TGS1_HUMAN
ID TGS1_HUMAN Reviewed; 853 AA.
AC Q96RS0; A6NJQ5; Q5GH23; Q8TDG9; Q96QU3; Q9H5V3;
DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 3.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Trimethylguanosine synthase;
DE EC=2.1.1.- {ECO:0000269|PubMed:18775984};
DE AltName: Full=CLL-associated antigen KW-2;
DE AltName: Full=Cap-specific guanine-N2 methyltransferase;
DE AltName: Full=Hepatocellular carcinoma-associated antigen 137;
DE AltName: Full=Nuclear receptor coactivator 6-interacting protein;
DE AltName: Full=PRIP-interacting protein with methyltransferase motif;
DE Short=PIMT;
DE Short=PIPMT;
GN Name=TGS1; Synonyms=HCA137, NCOA6IP, PIMT;
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], FUNCTION, INTERACTION WITH NCOA6, TISSUE
RP SPECIFICITY, AND VARIANT THR-16.
RC TISSUE=Liver;
RX PubMed=11517327; DOI=10.1073/pnas.181347498;
RA Zhu Y.-J., Qi C., Cao W.-Q., Yeldandi A.V., Rao M.S., Reddy J.K.;
RT "Cloning and characterization of PIMT, a protein with a methyltransferase
RT domain, which interacts with and enhances nuclear receptor coactivator PRIP
RT function.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:10380-10385(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT THR-16.
RX PubMed=12200376; DOI=10.1182/blood-2002-02-0513;
RA Krackhardt A.M., Witzens M., Harig S., Hodi F.S., Zauls A.J., Chessia M.,
RA Barrett P., Gribben J.G.;
RT "Identification of tumor-associated antigens in chronic lymphocytic
RT leukemia by SEREX.";
RL Blood 100:2123-2131(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT THR-16.
RX PubMed=12097419; DOI=10.4049/jimmunol.169.2.1102;
RA Wang Y., Han K.-J., Pang X.-W., Vaughan H.A., Qu W., Dong X.-Y.,
RA Peng J.-R., Zhao H.-T., Rui J.-A., Leng X.-S., Cebon J., Burgess A.W.,
RA Chen W.-F.;
RT "Large scale identification of human hepatocellular carcinoma-associated
RT antigens by autoantibodies.";
RL J. Immunol. 169:1102-1109(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 276-853.
RC TISSUE=Rhabdomyosarcoma;
RA Behrends U., Gotz C., Mautner J.;
RT "SEREX-defined rhabdomyosarcoma antigens.";
RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 574-853.
RC TISSUE=Urinary bladder;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 629-853.
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 [8]
RP SUBCELLULAR LOCATION.
RX PubMed=12032086; DOI=10.1093/emboj/21.11.2736;
RA Verheggen C., Lafontaine D.L.J., Samarsky D., Mouaikel J., Blanchard J.-M.,
RA Bordonne R., Bertrand E.;
RT "Mammalian and yeast U3 snoRNPs are matured in specific and related nuclear
RT compartments.";
RL EMBO J. 21:2736-2745(2002).
RN [9]
RP FUNCTION, AND INTERACTION WITH CREBBP; EP300 AND PPARBP.
RX PubMed=11912212; DOI=10.1074/jbc.m201739200;
RA Misra P., Qi C., Yu S., Shah S.H., Cao W.Q., Rao M.S., Thimmapaya B.,
RA Zhu Y., Reddy J.K.;
RT "Interaction of PIMT with transcriptional coactivators CBP, p300, and PBP
RT differential role in transcriptional regulation.";
RL J. Biol. Chem. 277:20011-20019(2002).
RN [10]
RP INTERACTION WITH EED, AND SUBCELLULAR LOCATION.
RX PubMed=12943661; DOI=10.1016/s0006-291x(03)01514-6;
RA Enuenlue I., Papai G., Cserpan I., Udvardy A., Jeang K.-T., Boros I.;
RT "Different isoforms of PRIP-interacting protein with methyltransferase
RT domain/trimethylguanosine synthase localize to the cytoplasm and nucleus.";
RL Biochem. Biophys. Res. Commun. 309:44-51(2003).
RN [11]
RP INTERACTION WITH SMN.
RX PubMed=12776181; DOI=10.1038/sj.embor.embor863;
RA Mouaikel J., Narayanan U., Verheggen C., Matera A.G., Bertrand E., Tazi J.,
RA Bordonne R.;
RT "Interaction between the small-nuclear-RNA cap hypermethylase and the
RT spinal muscular atrophy protein, survival of motor neuron.";
RL EMBO Rep. 4:616-622(2003).
RN [12]
RP FUNCTION.
RX PubMed=16687569; DOI=10.1091/mbc.e06-03-0247;
RA Lemm I., Girard C., Kuhn A.N., Watkins N.J., Schneider M., Bordonne R.,
RA Luehrmann R.;
RT "Ongoing U snRNP biogenesis is required for the integrity of Cajal
RT bodies.";
RL Mol. Biol. Cell 17:3221-3231(2006).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF PHE-655; THR-673; ASP-696; ASN-704; ASP-719; ASN-731;
RP SER-763; TRP-766; ARG-807 AND ASN-808.
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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-55; THR-60; SER-154 AND
RP SER-438, AND 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 [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-55; THR-60; SER-89; SER-154
RP AND SER-438, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-85 AND SER-89, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-89, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-55; SER-85; SER-89; SER-96;
RP SER-141; TYR-146; SER-154; SER-189; SER-412 AND SER-578, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.21 ANGSTROMS) OF 653-853.
RX PubMed=19307714; DOI=10.1107/s0907444909003102;
RA Monecke T., Dickmanns A., Strasser A., Ficner R.;
RT "Structure analysis of the conserved methyltransferase domain of human
RT trimethylguanosine synthase TGS1.";
RL Acta Crystallogr. D 65:332-338(2009).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 618-853 IN COMPLEX WITH
RP 7-METHYLGUANOSINE AND S-ADENOSYL-L-HOMOCYSTEINE, AND MUTAGENESIS OF SER-763
RP AND TRP-766.
RX PubMed=19386620; DOI=10.1093/nar/gkp249;
RA Monecke T., Dickmanns A., Ficner R.;
RT "Structural basis for m7G-cap hypermethylation of small nuclear, small
RT nucleolar and telomerase RNA by the dimethyltransferase TGS1.";
RL Nucleic Acids Res. 37:3865-3877(2009).
CC -!- FUNCTION: Catalyzes the 2 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 Hypermethylation of the m7G cap of U snRNAs leads to their
CC concentration in nuclear foci, their colocalization with coilin and the
CC formation of canonical Cajal bodies (CBs). Plays a role in
CC transcriptional regulation. {ECO:0000269|PubMed:11517327,
CC ECO:0000269|PubMed:11912212, ECO:0000269|PubMed:16687569,
CC ECO:0000269|PubMed:18775984}.
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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=30 uM for m(7)GDP {ECO:0000269|PubMed:18775984};
CC KM=5 uM for S-adenosyl-L-methionine {ECO:0000269|PubMed:18775984};
CC pH dependence:
CC Optimum pH is 8.5-9.5. {ECO:0000269|PubMed:18775984};
CC -!- SUBUNIT: May form homooligomers. Interacts with CREBBP/CBP, EED/WAIT1,
CC EP300/P300, NCOA6/PRIP, PPARBP/PBP and SMN.
CC {ECO:0000269|PubMed:11517327, ECO:0000269|PubMed:11912212,
CC ECO:0000269|PubMed:12776181, ECO:0000269|PubMed:12943661,
CC ECO:0000269|PubMed:19386620}.
CC -!- INTERACTION:
CC Q96RS0; P22087: FBL; NbExp=2; IntAct=EBI-949244, EBI-358318;
CC Q96RS0; Q9Y2X3: NOP58; NbExp=2; IntAct=EBI-949244, EBI-395469;
CC Q96RS0; Q86UR1-2: NOXA1; NbExp=3; IntAct=EBI-949244, EBI-12025760;
CC Q96RS0; P36508: ZNF76; NbExp=3; IntAct=EBI-949244, EBI-7254550;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12943661}. Nucleus,
CC Cajal body {ECO:0000305|PubMed:12032086}. Nucleus, nucleolus
CC {ECO:0000269|PubMed:12032086}. Note=A 90 kDa isoform is found in the
CC nucleus while a 55 kDa isoform is found in the cytoplasm and
CC colocalizes with the tubulin network. {ECO:0000269|PubMed:12943661}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. High expression in heart,
CC skeletal muscle, kidney, liver and placenta.
CC {ECO:0000269|PubMed:11517327}.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily.
CC Trimethylguanosine synthase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH11999.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB15516.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY028423; AAK27730.1; -; mRNA.
DR EMBL; AF432215; AAL99922.1; -; mRNA.
DR EMBL; AF286340; AAK83025.1; -; mRNA.
DR EMBL; AC100817; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AY534911; AAT02709.1; -; mRNA.
DR EMBL; BC011999; AAH11999.1; ALT_INIT; mRNA.
DR EMBL; AK026648; BAB15516.1; ALT_INIT; mRNA.
DR CCDS; CCDS34894.1; -.
DR RefSeq; NP_001304831.1; NM_001317902.1.
DR RefSeq; NP_079107.6; NM_024831.7.
DR PDB; 3EGI; X-ray; 2.21 A; A/B/C/D=653-853.
DR PDB; 3GDH; X-ray; 2.00 A; A/B/C=618-853.
DR PDBsum; 3EGI; -.
DR PDBsum; 3GDH; -.
DR AlphaFoldDB; Q96RS0; -.
DR SMR; Q96RS0; -.
DR BioGRID; 125179; 69.
DR DIP; DIP-49970N; -.
DR IntAct; Q96RS0; 43.
DR MINT; Q96RS0; -.
DR STRING; 9606.ENSP00000260129; -.
DR iPTMnet; Q96RS0; -.
DR PhosphoSitePlus; Q96RS0; -.
DR BioMuta; TGS1; -.
DR DMDM; 317373500; -.
DR EPD; Q96RS0; -.
DR jPOST; Q96RS0; -.
DR MassIVE; Q96RS0; -.
DR MaxQB; Q96RS0; -.
DR PaxDb; Q96RS0; -.
DR PeptideAtlas; Q96RS0; -.
DR PRIDE; Q96RS0; -.
DR ProteomicsDB; 78017; -.
DR Antibodypedia; 11709; 167 antibodies from 26 providers.
DR DNASU; 96764; -.
DR Ensembl; ENST00000260129.6; ENSP00000260129.5; ENSG00000137574.11.
DR GeneID; 96764; -.
DR KEGG; hsa:96764; -.
DR MANE-Select; ENST00000260129.6; ENSP00000260129.5; NM_024831.8; NP_079107.6.
DR UCSC; uc003xsj.5; human.
DR CTD; 96764; -.
DR DisGeNET; 96764; -.
DR GeneCards; TGS1; -.
DR HGNC; HGNC:17843; TGS1.
DR HPA; ENSG00000137574; Low tissue specificity.
DR MIM; 606461; gene.
DR neXtProt; NX_Q96RS0; -.
DR OpenTargets; ENSG00000137574; -.
DR PharmGKB; PA162405660; -.
DR VEuPathDB; HostDB:ENSG00000137574; -.
DR eggNOG; KOG2730; Eukaryota.
DR GeneTree; ENSGT00390000018056; -.
DR HOGENOM; CLU_016892_0_0_1; -.
DR InParanoid; Q96RS0; -.
DR OMA; VNKPMDE; -.
DR OrthoDB; 176302at2759; -.
DR PhylomeDB; Q96RS0; -.
DR TreeFam; TF313065; -.
DR PathwayCommons; Q96RS0; -.
DR Reactome; R-HSA-1368082; RORA activates gene expression.
DR Reactome; R-HSA-1368108; BMAL1:CLOCK,NPAS2 activates circadian gene expression.
DR Reactome; R-HSA-191859; snRNP Assembly.
DR Reactome; R-HSA-1989781; PPARA activates gene expression.
DR Reactome; R-HSA-2151201; Transcriptional activation of mitochondrial biogenesis.
DR Reactome; R-HSA-2426168; Activation of gene expression by SREBF (SREBP).
DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation.
DR Reactome; R-HSA-400206; Regulation of lipid metabolism by PPARalpha.
DR Reactome; R-HSA-400253; Circadian Clock.
DR Reactome; R-HSA-9707564; Cytoprotection by HMOX1.
DR Reactome; R-HSA-9707616; Heme signaling.
DR SignaLink; Q96RS0; -.
DR BioGRID-ORCS; 96764; 531 hits in 1084 CRISPR screens.
DR ChiTaRS; TGS1; human.
DR EvolutionaryTrace; Q96RS0; -.
DR GeneWiki; TGS1; -.
DR GenomeRNAi; 96764; -.
DR Pharos; Q96RS0; Tbio.
DR PRO; PR:Q96RS0; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q96RS0; protein.
DR Bgee; ENSG00000137574; Expressed in tendon of biceps brachii and 191 other tissues.
DR ExpressionAtlas; Q96RS0; baseline and differential.
DR Genevisible; Q96RS0; HS.
DR GO; GO:0015030; C:Cajal body; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0030532; C:small nuclear ribonucleoprotein complex; IC:BHF-UCL.
DR GO; GO:0008173; F:RNA methyltransferase activity; TAS:Reactome.
DR GO; GO:0071164; F:RNA trimethylguanosine synthase activity; IDA:BHF-UCL.
DR GO; GO:0036261; P:7-methylguanosine cap hypermethylation; IDA:BHF-UCL.
DR GO; GO:0009452; P:7-methylguanosine RNA capping; IEA:InterPro.
DR GO; GO:0022613; P:ribonucleoprotein complex biogenesis; IC:BHF-UCL.
DR GO; GO:0000387; P:spliceosomal snRNP assembly; TAS:Reactome.
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 3D-structure; Cytoplasm; Methyltransferase; Nucleus; Phosphoprotein;
KW Reference proteome; S-adenosyl-L-methionine; Transcription;
KW Transcription regulation; Transferase.
FT CHAIN 1..853
FT /note="Trimethylguanosine synthase"
FT /id="PRO_0000204468"
FT REGION 53..80
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 149..187
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 334..461
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 527..632
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 631..846
FT /note="Sufficient for catalytic activity"
FT COMPBIAS 334..402
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 403..434
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 543..567
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 568..582
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 719
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 766
FT /ligand="N(7)-methylguanosine"
FT /ligand_id="ChEBI:CHEBI:20794"
FT /evidence="ECO:0000269|PubMed:19386620"
FT MOD_RES 55
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 60
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 85
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 89
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 96
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 141
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 146
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 154
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 189
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 412
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 438
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 578
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 16
FT /note="I -> T (in dbSNP:rs1818)"
FT /evidence="ECO:0000269|PubMed:11517327,
FT ECO:0000269|PubMed:12097419, ECO:0000269|PubMed:12200376"
FT /id="VAR_024734"
FT VARIANT 160
FT /note="I -> V (in dbSNP:rs3213971)"
FT /id="VAR_024735"
FT VARIANT 299
FT /note="P -> S (in dbSNP:rs11986329)"
FT /id="VAR_056241"
FT VARIANT 511
FT /note="I -> T (in dbSNP:rs10100659)"
FT /id="VAR_024736"
FT VARIANT 576
FT /note="V -> I (in dbSNP:rs16922259)"
FT /id="VAR_024737"
FT VARIANT 595
FT /note="T -> A (in dbSNP:rs10109493)"
FT /id="VAR_056242"
FT VARIANT 754
FT /note="F -> C (in dbSNP:rs7823773)"
FT /id="VAR_024738"
FT MUTAGEN 655
FT /note="F->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:18775984"
FT MUTAGEN 673
FT /note="T->A: Decreases catalytic activity to 13 percent of
FT wild type."
FT /evidence="ECO:0000269|PubMed:18775984"
FT MUTAGEN 696
FT /note="D->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:18775984"
FT MUTAGEN 704
FT /note="N->A: Decreases catalytic activity to 5 percent of
FT wild type."
FT /evidence="ECO:0000269|PubMed:18775984"
FT MUTAGEN 719
FT /note="D->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:18775984"
FT MUTAGEN 731
FT /note="N->A: Decreases catalytic activity to 4 percent of
FT wild type."
FT /evidence="ECO:0000269|PubMed:18775984"
FT MUTAGEN 763
FT /note="S->A: Decreases catalytic activity to 26 percent of
FT wild type."
FT /evidence="ECO:0000269|PubMed:18775984,
FT ECO:0000269|PubMed:19386620"
FT MUTAGEN 766
FT /note="W->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:18775984,
FT ECO:0000269|PubMed:19386620"
FT MUTAGEN 807
FT /note="R->A: Decreases catalytic activity to 6 percent of
FT wild type."
FT /evidence="ECO:0000269|PubMed:18775984"
FT MUTAGEN 808
FT /note="N->A: Decreases catalytic activity to 11 percent of
FT wild type."
FT /evidence="ECO:0000269|PubMed:18775984"
FT CONFLICT 566
FT /note="Missing (in Ref. 1; AAK27730)"
FT /evidence="ECO:0000305"
FT CONFLICT 624
FT /note="N -> T (in Ref. 3; AAK83025)"
FT /evidence="ECO:0000305"
FT CONFLICT 628
FT /note="N -> T (in Ref. 3; AAK83025)"
FT /evidence="ECO:0000305"
FT CONFLICT 681
FT /note="I -> F (in Ref. 1; AAK27730)"
FT /evidence="ECO:0000305"
FT CONFLICT 771
FT /note="Y -> H (in Ref. 2; AAL99922)"
FT /evidence="ECO:0000305"
FT HELIX 636..640
FT /evidence="ECO:0007829|PDB:3GDH"
FT HELIX 642..644
FT /evidence="ECO:0007829|PDB:3GDH"
FT HELIX 645..649
FT /evidence="ECO:0007829|PDB:3GDH"
FT HELIX 651..654
FT /evidence="ECO:0007829|PDB:3GDH"
FT HELIX 658..660
FT /evidence="ECO:0007829|PDB:3GDH"
FT HELIX 666..671
FT /evidence="ECO:0007829|PDB:3GDH"
FT HELIX 675..688
FT /evidence="ECO:0007829|PDB:3GDH"
FT STRAND 692..696
FT /evidence="ECO:0007829|PDB:3GDH"
FT HELIX 703..710
FT /evidence="ECO:0007829|PDB:3GDH"
FT STRAND 714..720
FT /evidence="ECO:0007829|PDB:3GDH"
FT HELIX 722..734
FT /evidence="ECO:0007829|PDB:3GDH"
FT HELIX 738..740
FT /evidence="ECO:0007829|PDB:3GDH"
FT STRAND 741..746
FT /evidence="ECO:0007829|PDB:3GDH"
FT HELIX 748..751
FT /evidence="ECO:0007829|PDB:3GDH"
FT HELIX 752..754
FT /evidence="ECO:0007829|PDB:3GDH"
FT STRAND 758..762
FT /evidence="ECO:0007829|PDB:3GDH"
FT HELIX 769..773
FT /evidence="ECO:0007829|PDB:3GDH"
FT STRAND 774..777
FT /evidence="ECO:0007829|PDB:3GDH"
FT TURN 779..781
FT /evidence="ECO:0007829|PDB:3GDH"
FT STRAND 782..785
FT /evidence="ECO:0007829|PDB:3EGI"
FT HELIX 787..797
FT /evidence="ECO:0007829|PDB:3GDH"
FT STRAND 801..806
FT /evidence="ECO:0007829|PDB:3GDH"
FT HELIX 811..816
FT /evidence="ECO:0007829|PDB:3GDH"
FT STRAND 824..831
FT /evidence="ECO:0007829|PDB:3GDH"
FT STRAND 834..842
FT /evidence="ECO:0007829|PDB:3GDH"
FT HELIX 843..845
FT /evidence="ECO:0007829|PDB:3EGI"
SQ SEQUENCE 853 AA; 96620 MW; FF670AFBE0979443 CRC64;
MCCEKWSRVA EMFLFIEERE DCKILCLCSR AFVEDRKLYN LGLKGYYIRD SGNNSGDQAT
EEEEGGYSCG TAESHDSKGI GLDESELDSE AELMRSMGLP LQFGRITAHK DFEVSMNTRN
KVKIKKKKHQ KKYLDEIVQE SWRKEYEEDD ILASDDPSSI EQYENTRTYE LQSKKDTETE
NPPVENTLSP KLEITEKWEK YWNEYGGGLL WQSWQEKHPG QALSSEPWNF PDTKEEWEQH
YSQLYWYYLE QFQYWEAQGW TFDASQSCDT DTYTSKTEAD DKNDEKCMKV DLVSFPSSPI
MVDNDSSGTS DKDHSEILDG ISNIKLNSEE VTQSQLDSCT SHDGHQQLSE VSSKRECPAS
GQSEPRNGGT NEESNSSGNT NTDPPAEDSQ KSSGANTSKD RPHASGTDGD ESEEDPPEHK
PSKLKRSHEL DIDENPASDF DDSGSLLGFK YGSGQKYGGI PNFSHRQVRY LEKNVKLKSK
YLDMRRQIKM KNKHIFFTKE SEKPFFKKSK ILSKVEKFLT WVNKPMDEEA SQESSSHDNV
HDASTSSDSE EQDMSVKKGD DLLETNNPEP EKCQSVSSAG ELETENYERD SLLATVPDEQ
DCVTQEVPDS RQAETEAEVK KKKNKKKNKK VNGLPPEIAA VPELAKYWAQ RYRLFSRFDD
GIKLDREGWF SVTPEKIAEH IAGRVSQSFK CDVVVDAFCG VGGNTIQFAL TGMRVIAIDI
DPVKIALARN NAEVYGIADK IEFICGDFLL LASFLKADVV FLSPPWGGPD YATAETFDIR
TMMSPDGFEI FRLSKKITNN IVYFLPRNAD IDQVASLAGP GGQVEIEQNF LNNKLKTITA
YFGDLIRRPA SET
