Information on EC 2.1.1.348 - mRNA m6A methyltransferase

for references in articles please use BRENDA:EC2.1.1.348
Word Map on EC 2.1.1.348
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Select one or more organisms in this record:

The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.1.1.348
-
RECOMMENDED NAME
GeneOntology No.
mRNA m6A methyltransferase
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
S-adenosyl-L-methionine + adenine in mRNA = S-adenosyl-L-homocysteine + N6-methyladenine in mRNA
show the reaction diagram
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:adenine in mRNA methyltransferase
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
-
depletion of isoforms METTL3 and METTL14 leads to apoptosis in cancer cells
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + adenine in 5'-UACACUCGAUCU-GGACU-AAAGCUGCUC
homocysteine + 5'-UACACUCGAUCU-GG-(N6-methyl)ACU-AAAGCUGCUC
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + adenine in mRNA
S-adenosyl-L-homocysteine + N6-methyladenine in mRNA
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + adenine in mRNA
S-adenosyl-L-homocysteine + N6-methyladenine in mRNA
show the reaction diagram
-
-
-
-
?
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
levels of m6A and METTL3 are up-regulated in human dental pulp cells stimulated by lipopolysaccharide
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
nuclear speckles. Protein WTAP is required for nuclear speckle localization of METTL3 and METTL14
Manually annotated by BRENDA team
-
METTL3 associates with ribosomes
Manually annotated by BRENDA team
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
sumoylation
-
METTL3 is modified by SUMO1 mainly at lysine residues K177, K211, K212 and K215, which can be reduced by an SUMO1-specific protease SENP1. SUMOylation of METTL3 does not alter its stability, localization and interaction with METTL14 and WTAP, but significantly represses its m6A methytransferase activity resulting in the decrease of m6A levels in mRNAs
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
crystal structures of the complex of Mettl3/Mettl14 methyltransferase domains in apo form as well as with bound S-adenosylmethionine (SAM) or S-adenosylhomocysteine (SAH) in the catalytic site. The heterodimeric complex of methyltransferase domains, combined with CCCH motifs constitute the minimally required regions for creating m6A modifications in vitro. Mettl3 is the catalytically active subunit while Mettl14 plays a structural role critical for substrate recognition
-
crystal structures of the METTL3-METTL14 heterodimer with methyltransferase domains in the ligand-free, S-adenosyl methionine (AdoMet-)bound and S-adenosyl homocysteine (AdoHcy-)bound states, with resolutions of 1.9, 1.71 and 1.61 A, respectively. Both METTL3 and METTL14 adopt a class I methyltransferase fold and they interact with each other via an extensive hydrogen bonding network, generating a positively charged groove
-
solution structure for the zinc finger domain of catalytic subunit METTL3. The zinc finger domain specifically binds to an RNA containing 5'-GGACU-3' consensus sequence. The zinc finger domain contains two CCCH-type zinc fingers connected by an anti-parallel beta-sheet. The RNA-binding interface comprises basic residues from zinc finger 1 and hydrophobic residues from beta-sheet and zinc finger 2
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
-
expression in Expi293 cells
-
expression in HEK-293 cell
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D395A
-
change of the DPPW catalytic motif to APPW in METTL3, abrogates the ability of its complex with wild type METTL14 to methylate RNA
D395A/A398A
-
catalytically inactive
E192A
-
change of EPPL to APPL in METTL14, little effect on methylation capacity if wild type METTL3 is present
K177R/K211R/K212R/K215R
-
mutation in subunit METTL3. SUMOylation of the mutant is reduced compared to that of METTL3 wild-type in H1299 stable cell lines
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
-
radioactivity-based assays using 3H-S-adenosyl-L-methionine for kinetic characterization of m6A-RNA modifications by METTL3-14 complex and m6A-RNA demethylase ALKBH5. Assay conditions are suitable for screening for ligands in a 384-well format with Z' factors of 0.78 and 0.77, respectively
medicine
-
METTL3 expression is elevated in lung adenocarcinoma and promotes growth, survival, and invasion of human lung cancer cells