Modomics - A Database of RNA Modifications

ID Card:

Full name: Cap-specific mRNA (nucleoside-2'-O-)-methyltransferase 1
Synonym: hMTr1, FTSJD2, KIAA0082
GI: 74750894
Orf: FTSJD2, KIAA0082
COG: COG0293
UniProt: Q8N1G2
Structures: | 4N48 | 4N49 | 4N4A |
Alpha Fold Predicted Structure: AF-Q8N1G2-F1
Enzyme type: methyltransferase
Position of modification - modification: m:1 - GpppNm m:1 - GpppNmNm m:1 - m7GpppNm m:1 - m7GpppNmNm n:1 - GpppNm n:1 - GpppNmNm n:1 - m7GpppNm n:1 - m7GpppNmNm


PDB Structures:


4N48

Structure Description:

Title:
Classification:
Technique:

Abstract of the PDB Structure's related Publication:

The 5' cap of human messenger RNA contains 2'-O-methylation of the first and often second transcribed nucleotide that is important for its processing, translation and stability. Human enzymes that methylate these nucleotides, termed CMTr1 and CMTr2, respectively, have recently been identified. However, the structures of these enzymes and their mechanisms of action remain unknown. In the present study, we solve the crystal structures of the active CMTr1 catalytic domain in complex with a methyl group donor and a capped oligoribonucleotide, thereby revealing the mechanism of specific recognition of capped RNA. This mechanism differs significantly from viral enzymes, thus providing a framework for their specific targeting. Based on the crystal structure of CMTr1, a comparative model of the CMTr2 catalytic domain is generated. This model, together with mutational analysis, leads to the identification of residues involved in RNA and methyl group donor binding.

Download RCSB-PDB Structures:

Pdb Files   4N48.pdb   4N49.pdb   4N4A.pdb  
Pdbx/mmCIF Files   4N48.cif   4N49.cif   4N4A.cif  


Protein sequence:

MKRRTDPECTAPIKKQKKRVAELALSLSSTSDDEPPSSVSHGAKASTTSLSGSDSETEGKQHSSDSFDDAFKADSLVEGTSSRYSMYNSVSQKLMAKMGFREGEGLGKYSQGRKDIVEASSQKGRRGLGLTLRGFDQELNVDWRDEPEPSACEQVSWFPECTTEIPDTQEMSDWMVVGKRKMIIEDETEFCGEELLHSVLQCKSVFDVLDGEEMRRARTRANPYEMIRGVFFLNRAAMKMANMDFVFDRMFTNPRDSYGKPLVKDREAELLYFADVCAGPGGFSEYVLWRKKWHAKGFGMTLKGPNDFKLEDFYSASSELFEPYYGEGGIDGDGDITRPENISAFRNFVLDNTDRKGVHFLMADGGFSVEGQENLQEILSKQLLLCQFLMALSIVRTGGHFICKTFDLFTPFSVGLVYLLYCCFERVCLFKPITSRPANSERYVVCKGLKVGIDDVRDYLFAVNIKLNQLRNTDSDVNLVVPLEVIKGDHEFTDYMIRSNESHCSLQIKALAKIHAFVQDTTLSEPRQAEIRKECLRLWGIPDQARVAPSSSDPKSKFFELIQGTEIDIFSYKPTLLTSKTLEKIRPVFDYRCMVSGSEQKFLIGLGKSQIYTWDGRQSDRWIKLDLKTELPRDTLLSVEIVHELKGEGKAQRKISAIHILDVLVLNGTDVREQHFNQRIQLAEKFVKAVSKPSRPDMNPIRVKEVYRLEEMEKIFVRLEMKIIKGSSGTPKLSYTGRDDRHFVPMGLYIVRTVNEPWTMGFSKSFKKKFFYNKKTKDSTFDLPADSIAPFHICYYGRLFWEWGDGIRVHDSQKPQDQDKLSKEDVLSFIQMHRA

Comments:

hMTr1 protein transfers a methyl group from S-adenosylmethionine to the 2'-O-ribose of the first nucleotide of messenger RNA and small nuclear RNA. N(7) methylation of the guanosine cap is not required for hMTr1 activity. Cellular eukaryotic mRNAs are capped at their 5' ends with a 7-methlylguanosine nucleotide, that plays a pivotal role in conferring mRNA stability. 7-methylguanosine stimulates mRNA biogenesis, namely splicing, poly (A) addition, nucleoplasmatic transport, and increasing translational efficiency ( Werner et al. 2011 ).




Reaction Substrate SubstrateType Position Transcript Name Transcript Region Cellular Localization References
GpppN:GpppNm RNA snRNA 1 small nuclear RNA component of U1 snRNP capG : cap1 Nucleoplasm 21310715   
GpppN:GpppNm RNA snRNA 1 small nuclear RNA component of U2 snRNP capG : cap1 Nucleoplasm 21310715   
GpppN:GpppNm RNA mRNA 1 capG : cap1 Nucleoplasm 21310715   
m7GpppN:m7GpppNm RNA snRNA 1 small nuclear RNA component of U1 snRNP capG : cap1 Nucleoplasm 21310715   
m7GpppN:m7GpppNm RNA snRNA 1 small nuclear RNA component of U2 snRNP capG : cap1 Nucleoplasm 21310715   
m7GpppN:m7GpppNm RNA mRNA 1 capG : cap1 Nucleoplasm 21310715   
GpppNNm:GpppNmNm RNA snRNA 1 small nuclear RNA component of U1 snRNP capG : cap1 Nucleoplasm 21310715   
GpppNNm:GpppNmNm RNA snRNA 1 small nuclear RNA component of U2 snRNP capG : cap1 Nucleoplasm 21310715   
GpppNNm:GpppNmNm RNA mRNA 1 capG : cap1 Nucleoplasm 21310715   
m7GpppNmN:m7GpppNmNm RNA snRNA 1 small nuclear RNA component of U1 snRNP capG : cap1 Nucleoplasm 21310715   
m7GpppNmN:m7GpppNmNm RNA snRNA 1 small nuclear RNA component of U2 snRNP capG : cap1 Nucleoplasm 21310715   
m7GpppNmN:m7GpppNmNm RNA mRNA 1 capG : cap1 Nucleoplasm 21310715   

Alpha Fold Predicted Structure:






Clear Selection and Reset Camera

Protein sequence:

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

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-Q8N1G2-F1.pdb  
Alpha Fold Pdbx/mmCIF Files   AF-Q8N1G2-F1.cif  
DSSP Secondary Structures   Q8N1G2.dssp  





Publications:

Title Authors Journal Details PubMed Id DOI
Characterization of hMTr1, a human Cap1 2'-O-ribose methyltransferase. Belanger F, Stepinski J, Darzynkiewicz E, Pelletier J J Biol Chem [details] 20713356 -
The human interferon-regulated ISG95 protein interacts with RNA polymerase II and shows methyltransferase activity. Haline-Vaz T, Silva TC, Zanchin NI Biochem Biophys Res Commun [details] 18533109 -
Structural basis for m7G-cap hypermethylation of small nuclear, small nucleolar and telomerase RNA by the dimethyltransferase TGS1. Monecke T, Dickmanns A, Ficner R Nucleic Acids Res [details] 19386620 -

Links:

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