ID   TGS1_RAT                Reviewed;         850 AA.
AC   P85107;
DT   03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT   03-APR-2007, sequence version 1.
DT   27-MAR-2024, entry version 105.
DE   RecName: Full=Trimethylguanosine synthase;
DE            EC=2.1.1.- {ECO:0000250|UniProtKB:Q96RS0};
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 {ECO:0000250|UniProtKB:Q96RS0};
GN   Synonyms=Ncoa6ip {ECO:0000312|RGD:1309953}, Pimt
GN   {ECO:0000250|UniProtKB:Q96RS0};
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1] {ECO:0000305}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway {ECO:0000269|PubMed:15057822};
RX   PubMed=15057822; DOI=10.1038/nature02426;
RA   Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA   Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA   Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA   Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA   Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA   Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA   Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA   Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA   Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA   Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA   Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA   Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA   Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA   Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA   Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA   Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA   Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA   Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA   Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA   Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA   Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA   Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA   Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA   Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA   Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA   Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA   Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA   Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA   Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA   Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA   Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA   Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA   Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA   Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA   Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA   Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA   Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA   Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA   Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA   Mockrin S., Collins F.S.;
RT   "Genome sequence of the Brown Norway rat yields insights into mammalian
RT   evolution.";
RL   Nature 428:493-521(2004).
RN   [2] {ECO:0000305}
RP   TISSUE SPECIFICITY.
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   [3]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-431, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA   Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14 different rat
RT   organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
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 (By similarity).
CC       {ECO:0000250|UniProtKB:Q96RS0}.
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:0000250|UniProtKB:Q96RS0};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67621;
CC         Evidence={ECO:0000250|UniProtKB:Q96RS0};
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:0000250|UniProtKB:Q96RS0};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67625;
CC         Evidence={ECO:0000250|UniProtKB:Q96RS0};
CC   -!- SUBUNIT: May form homooligomers. Interacts with CREBBP/CBP, EED/WAIT1,
CC       EP300/P300, NCOA6/PRIP, PPARBP/PBP and SMN (By similarity).
CC       {ECO:0000250|UniProtKB:Q96RS0}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q96RS0}.
CC       Nucleus, Cajal body {ECO:0000250|UniProtKB:Q96RS0}. Nucleus, nucleolus
CC       {ECO:0000250|UniProtKB:Q96RS0}.
CC   -!- TISSUE SPECIFICITY: A 55 kDa isoform is widely expressed while a 90 kDa
CC       isoform is detected exclusively in brain and testis (at protein level).
CC       {ECO:0000269|PubMed:12943661}.
CC   -!- SIMILARITY: Belongs to the methyltransferase superfamily.
CC       Trimethylguanosine synthase family. {ECO:0000255}.
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DR   EMBL; AABR03040398; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   RefSeq; NP_001101374.1; NM_001107904.1.
DR   AlphaFoldDB; P85107; -.
DR   SMR; P85107; -.
DR   STRING; 10116.ENSRNOP00000010783; -.
DR   iPTMnet; P85107; -.
DR   PhosphoSitePlus; P85107; -.
DR   PaxDb; 10116-ENSRNOP00000010783; -.
DR   Ensembl; ENSRNOT00000010783.6; ENSRNOP00000010783.5; ENSRNOG00000008156.6.
DR   GeneID; 312947; -.
DR   KEGG; rno:312947; -.
DR   UCSC; RGD:1309953; rat.
DR   AGR; RGD:1309953; -.
DR   CTD; 96764; -.
DR   RGD; 1309953; Tgs1.
DR   eggNOG; KOG2730; Eukaryota.
DR   GeneTree; ENSGT00390000018056; -.
DR   HOGENOM; CLU_016892_0_0_1; -.
DR   InParanoid; P85107; -.
DR   OMA; GWETYWA; -.
DR   OrthoDB; 5473515at2759; -.
DR   PhylomeDB; P85107; -.
DR   TreeFam; TF313065; -.
DR   Reactome; R-RNO-191859; snRNP Assembly.
DR   Reactome; R-RNO-400206; Regulation of lipid metabolism by PPARalpha.
DR   Reactome; R-RNO-9707564; Cytoprotection by HMOX1.
DR   PRO; PR:P85107; -.
DR   Proteomes; UP000002494; Chromosome 5.
DR   Bgee; ENSRNOG00000008156; Expressed in thymus and 19 other cell types or tissues.
DR   GO; GO:0015030; C:Cajal body; IEA:UniProtKB-SubCell.
DR   GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR   GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR   GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; ISO:RGD.
DR   GO; GO:0071164; F:RNA trimethylguanosine synthase activity; ISO:RGD.
DR   GO; GO:0036261; P:7-methylguanosine cap hypermethylation; ISO:RGD.
DR   GO; GO:0009452; P:7-methylguanosine RNA capping; IEA:InterPro.
DR   CDD; cd02440; AdoMet_MTases; 1.
DR   Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1.
DR   InterPro; IPR019012; RNA_cap_Gua-N2-MeTrfase.
DR   InterPro; IPR029063; SAM-dependent_MTases_sf.
DR   PANTHER; PTHR14741; S-ADENOSYLMETHIONINE-DEPENDENT METHYLTRANSFERASE RELATED; 1.
DR   PANTHER; PTHR14741:SF32; TRIMETHYLGUANOSINE SYNTHASE; 1.
DR   Pfam; PF09445; Methyltransf_15; 1.
DR   SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1.
DR   Genevisible; P85107; RN.
PE   1: Evidence at protein level;
KW   Cytoplasm; Methyltransferase; Nucleus; Phosphoprotein; Reference proteome;
KW   S-adenosyl-L-methionine; Transcription; Transcription regulation;
KW   Transferase.
FT   CHAIN           1..850
FT                   /note="Trimethylguanosine synthase"
FT                   /id="PRO_0000283727"
FT   REGION          54..85
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          278..311
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          327..454
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          523..566
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          595..628
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        57..85
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        331..345
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        373..389
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        390..439
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        529..543
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        544..560
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         713
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250|UniProtKB:Q12052"
FT   MOD_RES         61
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96RS0"
FT   MOD_RES         92
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96RS0"
FT   MOD_RES         152
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96RS0"
FT   MOD_RES         405
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96RS0"
FT   MOD_RES         431
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         571
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96RS0"
SQ   SEQUENCE   850 AA;  96045 MW;  1C47E614F90382DD CRC64;
     MCCEKWSHVA EMLLFIEDRE EEYKILCLCS RAFVEDRKLY NLGLKGYYVK SSGNNAGDRV
     TEEEEDDHSS GTTESHSADE GDLDPEAKLM RSMGLPVRFG RMSTHGSFEV SMNARNKAKV
     RQKRRKHRKQ YLDEIVREDW RNDCEEDDLV VSDDPSSVEH CENNSACEIQ SKTDAEAENL
     PVENTLAPKL EVTENWEKYW NEYGEGLLWQ SWQEKYPDQT LSSEPWNLPD TKEEWEQHYS
     QLYWYYLEQF QYWEAQGWTF VASQNCDKDV CTSHTQVDQN AESSLKADGT TLSSSPNTAE
     DESLGSNDND HNEIIAGINK ITLSAEEVEQ SQLDSSEHCD KPLSEVTGKE CPASGGSDSC
     HGTPKESDIS ENRSSDQPAQ ELQESSGTNT SKHRPHHNGT DGNESEDDPP DHKPSKMKRS
     HELDIDENPD SEVDDNGFHL GFKHGSGQKY GGIPNFSRRQ VRYLEKNVKY KSKYLDMRKR
     MTVKNKHIVF SEESGKPFIR KSKVRSKVEK FLKWVNEPVD EEISQEPLSH NKMQDTCTSS
     DSEEQDMSME KTDGLMETRD PEPENCQTIS SASELEAEKS EGGSLVAAVP ENCSTEGVAN
     SPRAEAEVEI KKKKKKKKKN KNKKINGLPP EIASVPELAK YWAQRYRLFS RFDDGIKLDK
     EGWFSVTPEK IAEHIAGRVS QSFNCDIIVD AFCGVGGNTI QFALTGKRVI AIDIDPVKID
     LARNNAEVYG VADKIEFICG DFLLLAPCLK ADVVFLSPPW GGPDYATAET FDIRTMMSPD
     GFEIFRLSQK ITNNIVYFLP RNADVDQVAS LAGPGGQVEI EQNFLNNKLK TITAYFGDLI
     RRPALRSAEA
//