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Protein

Trimethylguanosine synthase

Gene

TGS1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalyzes the 2 serial methylation steps for the conversion of the 7-monomethylguanosine (m7G) caps of snRNAs and snoRNAs to a 2,2,7-trimethylguanosine (m(2,2,7)G) cap structure. The enzyme is specific for guanine, and N7 methylation must precede N2 methylation. Hypermethylation of the m7G cap of U snRNAs leads to their concentration in nuclear foci, their colocalization with coilin and the formation of canonical Cajal bodies (CBs). Plays a role in transcriptional regulation.4 Publications

Catalytic activityi

S-adenosyl-L-methionine + m7G(5')pppR-RNA = S-adenosyl-L-homocysteine + m(2,7)G(5')pppR-RNA.
S-adenosyl-L-methionine + m(2,7)G(5')pppR-RNA = S-adenosyl-L-homocysteine + m(2,2,7)G(5')pppR-RNA.

Kineticsi

  1. KM=30 µM for m7GDP1 Publication
  2. KM=5 µM for S-adenosyl-L-methionine1 Publication

    pH dependencei

    Optimum pH is 8.5-9.5.1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei719S-adenosyl-L-methionineBy similarity1
    Binding sitei7667-methylguanosine1 Publication1

    GO - Molecular functioni

    • RNA methyltransferase activity Source: Reactome
    • RNA trimethylguanosine synthase activity Source: BHF-UCL

    GO - Biological processi

    Keywordsi

    Molecular functionMethyltransferase, Transferase
    Biological processTranscription, Transcription regulation
    LigandS-adenosyl-L-methionine

    Enzyme and pathway databases

    ReactomeiR-HSA-1368082 RORA activates gene expression
    R-HSA-1368108 BMAL1:CLOCK,NPAS2 activates circadian gene expression
    R-HSA-191859 snRNP Assembly
    R-HSA-1989781 PPARA activates gene expression
    R-HSA-2151201 Transcriptional activation of mitochondrial biogenesis
    R-HSA-2426168 Activation of gene expression by SREBF (SREBP)
    R-HSA-381340 Transcriptional regulation of white adipocyte differentiation
    R-HSA-400206 Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)
    R-HSA-400253 Circadian Clock

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Trimethylguanosine synthase (EC:2.1.1.-)
    Alternative name(s):
    CLL-associated antigen KW-2
    Cap-specific guanine-N2 methyltransferase
    Hepatocellular carcinoma-associated antigen 137
    Nuclear receptor coactivator 6-interacting protein
    PRIP-interacting protein with methyltransferase motif
    Short name:
    PIMT
    Short name:
    PIPMT
    Gene namesi
    Name:TGS1
    Synonyms:HCA137, NCOA6IP, PIMT
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 8

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000137574.10
    HGNCiHGNC:17843 TGS1
    MIMi606461 gene
    neXtProtiNX_Q96RS0

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi655F → A: Loss of catalytic activity. 1 Publication1
    Mutagenesisi673T → A: Decreases catalytic activity to 13 percent of wild type. 1 Publication1
    Mutagenesisi696D → A: Loss of catalytic activity. 1 Publication1
    Mutagenesisi704N → A: Decreases catalytic activity to 5 percent of wild type. 1 Publication1
    Mutagenesisi719D → A: Loss of catalytic activity. 1 Publication1
    Mutagenesisi731N → A: Decreases catalytic activity to 4 percent of wild type. 1 Publication1
    Mutagenesisi763S → A: Decreases catalytic activity to 26 percent of wild type. 2 Publications1
    Mutagenesisi766W → A: Loss of catalytic activity. 2 Publications1
    Mutagenesisi807R → A: Decreases catalytic activity to 6 percent of wild type. 1 Publication1
    Mutagenesisi808N → A: Decreases catalytic activity to 11 percent of wild type. 1 Publication1

    Organism-specific databases

    DisGeNETi96764
    OpenTargetsiENSG00000137574
    PharmGKBiPA162405660

    Polymorphism and mutation databases

    BioMutaiTGS1
    DMDMi317373500

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00002044681 – 853Trimethylguanosine synthaseAdd BLAST853

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei55PhosphoserineCombined sources1
    Modified residuei60PhosphothreonineCombined sources1
    Modified residuei85PhosphoserineCombined sources1
    Modified residuei89PhosphoserineCombined sources1
    Modified residuei96PhosphoserineCombined sources1
    Modified residuei141PhosphoserineCombined sources1
    Modified residuei146PhosphotyrosineCombined sources1
    Modified residuei154PhosphoserineCombined sources1
    Modified residuei189PhosphoserineCombined sources1
    Modified residuei412PhosphoserineCombined sources1
    Modified residuei438PhosphoserineCombined sources1
    Modified residuei578PhosphoserineCombined sources1

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    EPDiQ96RS0
    MaxQBiQ96RS0
    PaxDbiQ96RS0
    PeptideAtlasiQ96RS0
    PRIDEiQ96RS0
    ProteomicsDBi78017

    PTM databases

    iPTMnetiQ96RS0
    PhosphoSitePlusiQ96RS0

    Expressioni

    Tissue specificityi

    Ubiquitously expressed. High expression in heart, skeletal muscle, kidney, liver and placenta.1 Publication

    Gene expression databases

    BgeeiENSG00000137574
    CleanExiHS_TGS1
    ExpressionAtlasiQ96RS0 baseline and differential
    GenevisibleiQ96RS0 HS

    Organism-specific databases

    HPAiHPA025024
    HPA029824

    Interactioni

    Subunit structurei

    May form homooligomers. Interacts with CREBBP/CBP, EED/WAIT1, EP300/P300, NCOA6/PRIP, PPARBP/PBP and SMN.5 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    NOP58Q9Y2X32EBI-949244,EBI-395469

    Protein-protein interaction databases

    BioGridi125179, 41 interactors
    DIPiDIP-49970N
    IntActiQ96RS0, 35 interactors
    MINTiQ96RS0
    STRINGi9606.ENSP00000260129

    Structurei

    Secondary structure

    1853
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi636 – 640Combined sources5
    Helixi642 – 644Combined sources3
    Helixi645 – 649Combined sources5
    Helixi651 – 654Combined sources4
    Helixi658 – 660Combined sources3
    Helixi666 – 671Combined sources6
    Helixi675 – 688Combined sources14
    Beta strandi692 – 696Combined sources5
    Helixi703 – 710Combined sources8
    Beta strandi714 – 720Combined sources7
    Helixi722 – 734Combined sources13
    Helixi738 – 740Combined sources3
    Beta strandi741 – 746Combined sources6
    Helixi748 – 751Combined sources4
    Helixi752 – 754Combined sources3
    Beta strandi758 – 762Combined sources5
    Helixi769 – 773Combined sources5
    Beta strandi774 – 777Combined sources4
    Turni779 – 781Combined sources3
    Beta strandi782 – 785Combined sources4
    Helixi787 – 797Combined sources11
    Beta strandi801 – 806Combined sources6
    Helixi811 – 816Combined sources6
    Beta strandi824 – 831Combined sources8
    Beta strandi834 – 842Combined sources9
    Helixi843 – 845Combined sources3

    3D structure databases

    ProteinModelPortaliQ96RS0
    SMRiQ96RS0
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ96RS0

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni631 – 846Sufficient for catalytic activityAdd BLAST216

    Compositional bias

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Compositional biasi611 – 624Lys-richAdd BLAST14

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiKOG2730 Eukaryota
    ENOG410XRUD LUCA
    GeneTreeiENSGT00390000018056
    HOGENOMiHOG000154561
    HOVERGENiHBG059797
    InParanoidiQ96RS0
    KOiK14292
    OMAiMNTRNKV
    OrthoDBiEOG091G0DYO
    PhylomeDBiQ96RS0
    TreeFamiTF313065

    Family and domain databases

    InterProiView protein in InterPro
    IPR019012 RNA_cap_Gua-N2-MeTrfase
    IPR029063 SAM-dependent_MTases
    PfamiView protein in Pfam
    PF09445 Methyltransf_15, 1 hit
    SUPFAMiSSF53335 SSF53335, 1 hit

    Sequencei

    Sequence statusi: Complete.

    Q96RS0-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MCCEKWSRVA EMFLFIEERE DCKILCLCSR AFVEDRKLYN LGLKGYYIRD
    60 70 80 90 100
    SGNNSGDQAT EEEEGGYSCG TAESHDSKGI GLDESELDSE AELMRSMGLP
    110 120 130 140 150
    LQFGRITAHK DFEVSMNTRN KVKIKKKKHQ KKYLDEIVQE SWRKEYEEDD
    160 170 180 190 200
    ILASDDPSSI EQYENTRTYE LQSKKDTETE NPPVENTLSP KLEITEKWEK
    210 220 230 240 250
    YWNEYGGGLL WQSWQEKHPG QALSSEPWNF PDTKEEWEQH YSQLYWYYLE
    260 270 280 290 300
    QFQYWEAQGW TFDASQSCDT DTYTSKTEAD DKNDEKCMKV DLVSFPSSPI
    310 320 330 340 350
    MVDNDSSGTS DKDHSEILDG ISNIKLNSEE VTQSQLDSCT SHDGHQQLSE
    360 370 380 390 400
    VSSKRECPAS GQSEPRNGGT NEESNSSGNT NTDPPAEDSQ KSSGANTSKD
    410 420 430 440 450
    RPHASGTDGD ESEEDPPEHK PSKLKRSHEL DIDENPASDF DDSGSLLGFK
    460 470 480 490 500
    YGSGQKYGGI PNFSHRQVRY LEKNVKLKSK YLDMRRQIKM KNKHIFFTKE
    510 520 530 540 550
    SEKPFFKKSK ILSKVEKFLT WVNKPMDEEA SQESSSHDNV HDASTSSDSE
    560 570 580 590 600
    EQDMSVKKGD DLLETNNPEP EKCQSVSSAG ELETENYERD SLLATVPDEQ
    610 620 630 640 650
    DCVTQEVPDS RQAETEAEVK KKKNKKKNKK VNGLPPEIAA VPELAKYWAQ
    660 670 680 690 700
    RYRLFSRFDD GIKLDREGWF SVTPEKIAEH IAGRVSQSFK CDVVVDAFCG
    710 720 730 740 750
    VGGNTIQFAL TGMRVIAIDI DPVKIALARN NAEVYGIADK IEFICGDFLL
    760 770 780 790 800
    LASFLKADVV FLSPPWGGPD YATAETFDIR TMMSPDGFEI FRLSKKITNN
    810 820 830 840 850
    IVYFLPRNAD IDQVASLAGP GGQVEIEQNF LNNKLKTITA YFGDLIRRPA

    SET
    Length:853
    Mass (Da):96,620
    Last modified:January 11, 2011 - v3
    Checksum:iFF670AFBE0979443
    GO

    Sequence cautioni

    The sequence AAH11999 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
    The sequence BAB15516 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti566Missing in AAK27730 (PubMed:11517327).Curated1
    Sequence conflicti624N → T in AAK83025 (PubMed:12097419).Curated1
    Sequence conflicti628N → T in AAK83025 (PubMed:12097419).Curated1
    Sequence conflicti681I → F in AAK27730 (PubMed:11517327).Curated1
    Sequence conflicti771Y → H in AAL99922 (PubMed:12200376).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_02473416I → T3 PublicationsCorresponds to variant dbSNP:rs1818Ensembl.1
    Natural variantiVAR_024735160I → V. Corresponds to variant dbSNP:rs3213971Ensembl.1
    Natural variantiVAR_056241299P → S. Corresponds to variant dbSNP:rs11986329Ensembl.1
    Natural variantiVAR_024736511I → T. Corresponds to variant dbSNP:rs10100659Ensembl.1
    Natural variantiVAR_024737576V → I. Corresponds to variant dbSNP:rs16922259Ensembl.1
    Natural variantiVAR_056242595T → A. Corresponds to variant dbSNP:rs10109493Ensembl.1
    Natural variantiVAR_024738754F → C. Corresponds to variant dbSNP:rs7823773Ensembl.1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AY028423 mRNA Translation: AAK27730.1
    AF432215 mRNA Translation: AAL99922.1
    AF286340 mRNA Translation: AAK83025.1
    AC100817 Genomic DNA No translation available.
    AY534911 mRNA Translation: AAT02709.1
    BC011999 mRNA Translation: AAH11999.1 Different initiation.
    AK026648 mRNA Translation: BAB15516.1 Different initiation.
    CCDSiCCDS34894.1
    RefSeqiNP_001304831.1, NM_001317902.1
    NP_079107.6, NM_024831.7
    UniGeneiHs.335068

    Genome annotation databases

    EnsembliENST00000260129; ENSP00000260129; ENSG00000137574
    GeneIDi96764
    KEGGihsa:96764
    UCSCiuc003xsj.5 human

    Keywords - Coding sequence diversityi

    Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiTGS1_HUMAN
    AccessioniPrimary (citable) accession number: Q96RS0
    Secondary accession number(s): A6NJQ5
    , Q5GH23, Q8TDG9, Q96QU3, Q9H5V3
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 20, 2005
    Last sequence update: January 11, 2011
    Last modified: July 18, 2018
    This is version 145 of the entry and version 3 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 8
      Human chromosome 8: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

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