Modomics - A Database of RNA Modifications

ID Card:

Full name:	trimethylguanosinesynthase 1
Synonym:	PRIP-interacting protein with methyltransferase motif (PIMT)
GI:	317373500
Orf:	TGS1
COG:	COG2263
UniProt:	Q96RS0
Structures:	\| 3EGI \| 3GDH \|
Alpha Fold Predicted Structure:	AF-Q96RS0-F1
Enzyme type:	methyltransferase
Position of modification - modification:	n:0 - m2,2,7GpppN snoRNA:0 - m2,2,7GpppN

PDB Structures:

3EGI

Structure Description:

Title:
Classification:
Technique:

Abstract of the PDB Structure's related Publication:

Methyltransferases play an important role in the post-transcriptional maturation of most ribonucleic acids. The modification of spliceosomal UsnRNAs includes N2-dimethylation of the m(7)G cap catalyzed by trimethylguanosine synthase 1 (TGS1). This 5'-cap hypermethylation occurs during the biogenesis of UsnRNPs as it initiates the m(3)G cap-dependent nuclear import of UsnRNPs. The conserved methyltransferase domain of human TGS1 has been purified, crystallized and the crystal structure of this domain with bound substrate m(7)GpppA was solved by means of multiple-wavelength anomalous dispersion. Crystal structure analysis revealed that m(7)GpppA binds via its adenosine moiety to the structurally conserved adenosylmethionine-binding pocket, while the m(7) guanosine remains unbound. This unexpected binding only occurs in the absence of AdoMet and suggests an incomplete binding pocket for the m(7)G cap which is caused by the N-terminal truncation of the protein. These structural data are consistent with the finding that the crystallized fragment of human TGS1 is catalytically inactive, while a fragment that is 17 amino acids longer exhibits activity.

Download RCSB-PDB Structures:

Pdb Files	3EGI.pdb 3GDH.pdb
Pdbx/mmCIF Files	3EGI.cif 3GDH.cif

Protein sequence:

MCCEKWSRVAEMFLFIEEREDCKILCLCSRAFVEDRKLYNLGLKGYYIRDSGNNSGDQATEEEEGGYSCGTAESHDSKGIGLDESELDSEAELMRSMGLPLQFGRITAHKDFEVSMNTRNKVKIKKKKHQKKYLDEIVQESWRKEYEEDDILASDDPSSIEQYENTRTYELQSKKDTETENPPVENTLSPKLEITEKWEKYWNEYGGGLLWQSWQEKHPGQALSSEPWNFPDTKEEWEQHYSQLYWYYLEQFQYWEAQGWTFDASQSCDTDTYTSKTEADDKNDEKCMKVDLVSFPSSPIMVDNDSSGTSDKDHSEILDGISNIKLNSEEVTQSQLDSCTSHDGHQQLSEVSSKRECPASGQSEPRNGGTNEESNSSGNTNTDPPAEDSQKSSGANTSKDRPHASGTDGDESEEDPPEHKPSKLKRSHELDIDENPASDFDDSGSLLGFKYGSGQKYGGIPNFSHRQVRYLEKNVKLKSKYLDMRRQIKMKNKHIFFTKESEKPFFKKSKILSKVEKFLTWVNKPMDEEASQESSSHDNVHDASTSSDSEEQDMSVKKGDDLLETNNPEPEKCQSVSSAGELETENYERDSLLATVPDEQDCVTQEVPDSRQAETEAEVKKKKNKKKNKKVNGLPPEIAAVPELAKYWAQRYRLFSRFDDGIKLDREGWFSVTPEKIAEHIAGRVSQSFKCDVVVDAFCGVGGNTIQFALTGMRVIAIDIDPVKIALARNNAEVYGIADKIEFICGDFLLLASFLKADVVFLSPPWGGPDYATAETFDIRTMMSPDGFEIFRLSKKITNNIVYFLPRNADIDQVASLAGPGGQVEIEQNFLNNKLKTITAYFGDLIRRPASET

Comments:

Catalyzes the two sequential 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. Some selenoprotein mRNAs were found to contain 2,2,7-trimethylguanosine (m(2,2,7)G) cap structure and Tgs1 was found to be involved in hypermethylation of these caps.

Reaction	Substrate	SubstrateType	References
m7GpppN:m2,7GpppN	snRNA (sn)	U1	18775984
m7GpppN:m2,7GpppN	snRNA (sn)	U2//	18775984
m7GpppN:m2,7GpppN	snRNA (sn)	U4//	18775984
m7GpppN:m2,7GpppN	snoRNA (sno)	U3//nucleus	18775984
m7GpppN:m2,7GpppN	snoRNA (sno)	snR10//nucleus	18775984
m7GpppN:m2,7GpppN	snoRNA (sno)	snR30//nucleus	18775984
m2,7GpppN:m2,2,7GpppN	snRNA (sn)	U1	18775984
m2,7GpppN:m2,2,7GpppN	snRNA (sn)	U2//	18775984
m2,7GpppN:m2,2,7GpppN	snRNA (sn)	U4//	18775984
m2,7GpppN:m2,2,7GpppN	snoRNA (sno)	U3//nucleus	18775984
m2,7GpppN:m2,2,7GpppN	snoRNA (sno)	snR10//nucleus	18775984
m2,7GpppN:m2,2,7GpppN	snoRNA (sno)	snR30//nucleus	18775984

Alpha Fold Predicted Structure:

Clear Selection and Reset Camera

Protein sequence:

M C C E K W S R V A E M F L F I E E R E D C K I L C L C S R A F V E D R K L Y N L G L K G Y Y I R D S G N N S G D Q A T E E E E G G Y S C G T A E S H D S K G I G L D E S E L D S E A E L M R S M G L P L Q F G R I T A H K D F E V S M N T R N K V K I K K K K H Q K K Y L D E I V Q E S W R K E Y E E D D I L A S D D P S S I E Q Y E N T R T Y E L Q S K K D T E T E N P P V E N T L S P K L E I T E K W E K Y W N E Y G G G L L W Q S W Q E K H P G Q A L S S E P W N F P D T K E E W E Q H Y S Q L Y W Y Y L E Q F Q Y W E A Q G W T F D A S Q S C D T D T Y T S K T E A D D K N D E K C M K V D L V S F P S S P I M V D N D S S G T S D K D H S E I L D G I S N I K L N S E E V T Q S Q L D S C T S H D G H Q Q L S E V S S K R E C P A S G Q S E P R N G G T N E E S N S S G N T N T D P P A E D S Q K S S G A N T S K D R P H A S G T D G D E S E E D P P E H K P S K L K R S H E L D I D E N P A S D F D D S G S L L G F K Y G S G Q K Y G G I P N F S H R Q V R Y L E K N V K L K S K Y L D M R R Q I K M K N K H I F F T K E S E K P F F K K S K I L S K V E K F L T W V N K P M D E E A S Q E S S S H D N V H D A S T S S D S E E Q D M S V K K G D D L L E T N N P E P E K C Q S V S S A G E L E T E N Y E R D S L L A T V P D E Q D C V T Q E V P D S R Q A E T E A E V K K K K N K K K N K K V N G L P P E I A A V P E L A K Y W A Q R Y R L F S R F D D G I K L D R E G W F S V T P E K I A E H I A G R V S Q S F K C D V V V D A F C G V G G N T I Q F A L T G M R V I A I D I D P V K I A L A R N N A E V Y G I A D K I E F I C G D F L L L A S F L K A D V V F L S P P W G G P D Y A T A E T F D I R T M M S P D G F E I F R L S K K I T N N I V Y F L P R N A D I D Q V A S L A G P G G Q V E I E Q N F L N N K L K T I T A Y F G D L I R R P A S E T

Secondary Structure Alphabet

G: 3-turn helix (3₁₀helix)
H: α-helix
I: 𝝅-helix (5 - turn helix)
T: Hydrogen Bonded Turn
B: β-sheet
S: Bend
C: Coil (residues not present in any of the above conformations)
N: Not assigned

Download PDB Structures & DSSP Secondary Structures:

Alpha Fold Pdb Files	AF-Q96RS0-F1.pdb
Alpha Fold Pdbx/mmCIF Files	AF-Q96RS0-F1.cif

Publications:

Title	Authors	Journal	Details	PubMed Id	DOI
Genetic and biochemical analysis of yeast and human cap trimethylguanosine synthase: functional overlap of 2,2,7-trimethylguanosine caps, small nuclear ribonucleoprotein components, pre-mRNA splicing factors, and RNA decay pathways.	Hausmann S, Zheng S, Costanzo M, Brost RL, Garcin D, Boone C, Shuman S, Schwer B	J Biol Chem	[details]	18775984	-
Structure analysis of the conserved methyltransferase domain of human trimethylguanosine synthase TGS1.	Monecke T, Dickmanns A, Strasser A, Ficner R	Acta Crystallogr D Biol Crystallogr	[details]	19307714	-
Hypermethylated-capped selenoprotein mRNAs in mammals.	Wurth L, Gribling-Burrer AS, Verheggen C, Leichter M, Takeuchi A, Baudrey S, Martin F, Krol A, Bertrand E, Allmang C...	Nucleic Acids Res	[details]	25013170	-