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Information on EC 2.1.1.229 - tRNA (carboxymethyluridine34-5-O)-methyltransferase
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EC Tree
2.1.1.229 tRNA (carboxymethyluridine34-5-O)-methyltransferaseIUBMB Comments
The enzyme catalyses the posttranslational modification of uridine residues at the wobble position 34 of the anticodon loop of tRNA.
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Word Map
- 2.1.1.229
-
wobble
- methyltransferases
-
5-methoxycarbonylmethyluridine
- ribonucleotide
-
anticodon
-
gene-specific
- trnagluuuc
-
translationally
- medicine
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Reaction Schemes
+
=
+
+
carboxymethyluridine34 in tRNA
=
+
5-(2-methoxy-2-oxoethyl)uridine34 in tRNA
Synonyms
trna methyltransferase 9, trm9p, trm9-trm112, yml014w, 
more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ALKBH8
MnmC
Trm9
Trm9p
TrmC
YfcK
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
S-adenosyl-L-methionine + carboxymethyluridine34 in tRNA = S-adenosyl-L-homocysteine + 5-(2-methoxy-2-oxoethyl)uridine34 in tRNA
S-adenosyl-L-methionine + carboxymethyluridine34 in tRNA = S-adenosyl-L-homocysteine + 5-(2-methoxy-2-oxoethyl)uridine34 in tRNA
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-
-
-
S-adenosyl-L-methionine + carboxymethyluridine34 in tRNA = S-adenosyl-L-homocysteine + 5-(2-methoxy-2-oxoethyl)uridine34 in tRNA
aspects of substrate recognition and catalytic mechanism. overview
S-adenosyl-L-methionine + carboxymethyluridine34 in tRNA = S-adenosyl-L-homocysteine + 5-(2-methoxy-2-oxoethyl)uridine34 in tRNA
the C-terminal domain catalyzes the FAD-dependent oxidation of the Calpha-N bond in carboxymethylaminomethyl uridine34. The resulting imine intermediate is (presumably) non-enzymatically hydrolyzes to 5-aminomethyl uridine, followed by S-adenosyl Lmethionine-dependent methylation to yield methylaminomethyl uridine34 in the N-terminal domain active site
S-adenosyl-L-methionine + carboxymethyluridine34 in tRNA = S-adenosyl-L-homocysteine + 5-(2-methoxy-2-oxoethyl)uridine34 in tRNA
the C-terminal domain catalyzes the FAD-dependent oxidation of the Calpha-N bond in carboxymethylaminomethyl uridine34. The resulting imine intermediate is (presumably) non-enzymatically hydrolyzes to 5-aminomethyl uridine, followed by S-adenosyl-L-methionine-dependent methylation to yield methylaminomethyl uridine34 in the N-terminal domain active site
-
S-adenosyl-L-methionine + carboxymethyluridine34 in tRNA = S-adenosyl-L-homocysteine + 5-(2-methoxy-2-oxoethyl)uridine34 in tRNA
the C-terminal domain catalyzes the FAD-dependent oxidation of the Calpha-N bond in carboxymethylaminomethyl uridine34. The resulting imine intermediate is (presumably) non-enzymatically hydrolyzes to 5-aminomethyl uridine, followed by S-adenosyl Lmethionine-dependent methylation to yield methylaminomethyl uridine34 in the N-terminal domain active site
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-
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PATHWAY SOURCE
PATHWAYS
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,
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SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:tRNA (carboxymethyluridine34-5-O)-methyltransferase
The enzyme catalyses the posttranslational modification of uridine residues at the wobble position 34 of the anticodon loop of tRNA.
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + carboxymethyl-2-thiouridine34 in tRNA
S-adenosyl-L-homocysteine + 5-(2-methoxy-2-oxoethyl)-2-thiouridine34 in tRNA
-
Trm9-Trm112, subunit Trm112 is required for the activity, but role of Sc Trm112 in the complex is not for catalysis
-
-
?
S-adenosyl-L-methionine + carboxymethylaminomethyl 2-thiouridine34 in tRNAGlu
S-adenosyl-L-homocysteine + methylaminomethyl 2-thiouridine34 in tRNAGlu + hydroxyacetate
S-adenosyl-L-methionine + carboxymethylaminomethyl 2-thiouridine34 in tRNALys
S-adenosyl-L-homocysteine + methylaminomethyl 2-thiouridine34 in tRNALys + hydroxyacetate
S-adenosyl-L-methionine + carboxymethylaminomethyl uridine34 in tRNAArg
S-adenosyl-L-homocysteine + methylaminomethyl uridine34 in tRNAArg + hydroxyacetate
S-adenosyl-L-methionine + carboxymethyluridine34 in tRNA
S-adenosyl-L-homocysteine + 5-(2-methoxy-2-oxoethyl)uridine34 in tRNA
S-adenosyl-L-methionine + carboxymethyluridine34 in tRNAArg3
S-adenosyl-L-homocysteine + 5-(2-methoxy-2-oxoethyl)uridine34 in tRNA
-
-
-
?
S-adenosyl-L-methionine + carboxymethyluridine34 in tRNAGlU
S-adenosyl-L-homocysteine + 5-(2-methoxy-2-oxoethyl)uridine34 in tRNA
-
-
-
?
S-adenosyl-S-carboxymethyl-L-homocysteine + 5-methoxyuridine34 in tRNA
S-adenosyl-L-methionine + uridine 5-oxyacetic acid in tRNA
proposed modification pathway of 5-oxyuridine derivatives, overview
-
-
?
S-adenosyl-L-methionine + carboxymethylaminomethyl 2-thiouridine34 in tRNAGlu
S-adenosyl-L-homocysteine + methylaminomethyl 2-thiouridine34 in tRNAGlu + hydroxyacetate
-
-
-
-
?
S-adenosyl-L-methionine + carboxymethylaminomethyl 2-thiouridine34 in tRNAGlu
S-adenosyl-L-homocysteine + methylaminomethyl 2-thiouridine34 in tRNAGlu + hydroxyacetate
-
-
-
?
S-adenosyl-L-methionine + carboxymethylaminomethyl 2-thiouridine34 in tRNAGlu
S-adenosyl-L-homocysteine + methylaminomethyl 2-thiouridine34 in tRNAGlu + hydroxyacetate
-
-
-
?
S-adenosyl-L-methionine + carboxymethylaminomethyl 2-thiouridine34 in tRNALys
S-adenosyl-L-homocysteine + methylaminomethyl 2-thiouridine34 in tRNALys + hydroxyacetate
-
-
-
-
?
S-adenosyl-L-methionine + carboxymethylaminomethyl 2-thiouridine34 in tRNALys
S-adenosyl-L-homocysteine + methylaminomethyl 2-thiouridine34 in tRNALys + hydroxyacetate
-
-
-
?
S-adenosyl-L-methionine + carboxymethylaminomethyl 2-thiouridine34 in tRNALys
S-adenosyl-L-homocysteine + methylaminomethyl 2-thiouridine34 in tRNALys + hydroxyacetate
-
-
-
?
S-adenosyl-L-methionine + carboxymethylaminomethyl uridine34 in tRNAArg
S-adenosyl-L-homocysteine + methylaminomethyl uridine34 in tRNAArg + hydroxyacetate
-
-
-
-
?
S-adenosyl-L-methionine + carboxymethylaminomethyl uridine34 in tRNAArg
S-adenosyl-L-homocysteine + methylaminomethyl uridine34 in tRNAArg + hydroxyacetate
-
-
-
?
S-adenosyl-L-methionine + carboxymethylaminomethyl uridine34 in tRNAArg
S-adenosyl-L-homocysteine + methylaminomethyl uridine34 in tRNAArg + hydroxyacetate
-
-
-
?
S-adenosyl-L-methionine + carboxymethyluridine34 in tRNA
S-adenosyl-L-homocysteine + 5-(2-methoxy-2-oxoethyl)uridine34 in tRNA
-
-
-
?
S-adenosyl-L-methionine + carboxymethyluridine34 in tRNA
S-adenosyl-L-homocysteine + 5-(2-methoxy-2-oxoethyl)uridine34 in tRNA
residue Arg567 os involved in tRNA substrate recognition
-
-
?
S-adenosyl-L-methionine + carboxymethyluridine34 in tRNA
S-adenosyl-L-homocysteine + 5-(2-methoxy-2-oxoethyl)uridine34 in tRNA
the enzyme catalyzes tRNA methylation to generate 5-methylcarboxymethyl uridine at the wobble position of certain tRNAs, a critical anticodon loop modification linked to DNA damage survival
-
-
?
S-adenosyl-L-methionine + carboxymethyluridine34 in tRNA
S-adenosyl-L-homocysteine + 5-(2-methoxy-2-oxoethyl)uridine34 in tRNA
ABH8 catalyzes RNA methylation through its methyltransferase domain. ABH8 MT domain alone exhibited weak methylase activity
5-(2-methoxy-2-oxoethyl)uridine i.e. 5-methoxycarboxymethyluridine
-
?
S-adenosyl-L-methionine + carboxymethyluridine34 in tRNA
S-adenosyl-L-homocysteine + 5-(2-methoxy-2-oxoethyl)uridine34 in tRNA
-
-
-
-
?
S-adenosyl-L-methionine + carboxymethyluridine34 in tRNA
S-adenosyl-L-homocysteine + 5-(2-methoxy-2-oxoethyl)uridine34 in tRNA
Trm9 methylates the uridine wobble base of tRNAArg(UCU) and tRNAGlU(UUC)
-
-
?
S-adenosyl-L-methionine + carboxymethyluridine34 in tRNA
S-adenosyl-L-homocysteine + 5-(2-methoxy-2-oxoethyl)uridine34 in tRNA
Trm9 methylates the uridine wobble base of tRNAGlU(UUC)
-
-
?
S-adenosyl-L-methionine + carboxymethyluridine34 in tRNA
S-adenosyl-L-homocysteine + 5-(2-methoxy-2-oxoethyl)uridine34 in tRNA
-
Trm9-Trm112, subunit Trm112 is required for the activity, but role of Sc Trm112 in the complex is not for catalysis
-
-
?
additional information
?
-
the bifunctional enzyme MnmC catalyzes the two consecutive reactions that convert 5-carboxymethylaminomethyl uridine to 5-methylaminomethyl uridine. The C-terminal domain of MnmC is responsible for the FAD-dependent deacetylation of cmnm5U to 5-aminomethyl uridine, whereas the N-terminal domain catalyzes the subsequent S-adenosyl-L-methionine-dependent methylation of 5-aminomethyl uridine, leading to the final product, 5-methylaminomethyl uridine, coordination of the two consecutive reactions, overview
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-
?
additional information
?
-
-
methylaminomethyl modification of uridine or 2-thiouridine (mnm5U34 or mnm5s2U34) at the wobble position of tRNAs specific for glutamate, lysine and arginine are observed in Escherichia coli and allow for specific recognition of codons ending in A or G. In the biosynthetic pathway responsible for this posttranscriptional modification, the bifunctional enzyme MnmC catalyzes the conversion of its hypermodified substrate carboxymethylaminomethyl uridine (cmnm5U34) to mnm5U34. MnmC catalyzes the FAD-dependent oxidative cleavage of carboxymethyl group from cmnm5U34 via an imine intermediate to generate aminomethyl uridine (nm5U34), which is subsequently methylated by S-adenosyl-L-methionine to yield methylaminomethyl uridine (mnm5U34)
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-
?
additional information
?
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alternative mechanisms in formation of the 5-carboxymethyluridine34 side chain at wobble position, overview
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-
?
additional information
?
-
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recombinant tagged Sc Trm9 protein purified from yeast methylates a saponified tRNA extract, demonstrating that Sc Trm9 is required for formation of the terminal methyl group of mcm5U
-
-
?
additional information
?
-
methylaminomethyl modification of uridine or 2-thiouridine (mnm5U34 or mnm5s2U34) at the wobble position of tRNAs specific for glutamate, lysine and arginine are observed in Escherichia coli and allow for specific recognition of codons ending in A or G. In the biosynthetic pathway responsible for this posttranscriptional modification, the bifunctional enzyme MnmC catalyzes the conversion of its hypermodified substrate carboxymethylaminomethyl uridine (cmnm5U34) to mnm5U34. MnmC catalyzes the FAD-dependent oxidative cleavage of carboxymethyl group from cmnm5U34 via an imine intermediate to generate aminomethyl uridine (nm5U34), which is subsequently methylated by S-adenosyl-L-methionine to yield methylaminomethyl uridine (mnm5U34)
-
-
?
additional information
?
-
methylaminomethyl modification of uridine or 2-thiouridine (mnm5U34 or mnm5s2U34) at the wobble position of tRNAs specific for glutamate, lysine and arginine are observed in Escherichia coli and allow for specific recognition of codons ending in A or G. In the biosynthetic pathway responsible for this posttranscriptional modification, the bifunctional enzyme MnmC catalyzes the conversion of its hypermodified substrate carboxymethylaminomethyl uridine (cmnm5U34) to mnm5U34. MnmC catalyzes the FAD-dependent oxidative cleavage of carboxymethyl group from cmnm5U34 via an imine intermediate to generate aminomethyl uridine (nm5U34), which is subsequently methylated by S-adenosyl-L-methionine to yield methylaminomethyl uridine (mnm5U34)
-
-
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + carboxymethyl-2-thiouridine34 in tRNA
S-adenosyl-L-homocysteine + 5-(2-methoxy-2-oxoethyl)-2-thiouridine34 in tRNA
-
Trm9-Trm112, subunit Trm112 is required for the activity, but role of Sc Trm112 in the complex is not for catalysis
-
-
?
S-adenosyl-L-methionine + carboxymethylaminomethyl 2-thiouridine34 in tRNAGlu
S-adenosyl-L-homocysteine + methylaminomethyl 2-thiouridine34 in tRNAGlu + hydroxyacetate
S-adenosyl-L-methionine + carboxymethylaminomethyl 2-thiouridine34 in tRNALys
S-adenosyl-L-homocysteine + methylaminomethyl 2-thiouridine34 in tRNALys + hydroxyacetate
S-adenosyl-L-methionine + carboxymethylaminomethyl uridine34 in tRNAArg
S-adenosyl-L-homocysteine + methylaminomethyl uridine34 in tRNAArg + hydroxyacetate
S-adenosyl-L-methionine + carboxymethyluridine34 in tRNA
S-adenosyl-L-homocysteine + 5-(2-methoxy-2-oxoethyl)uridine34 in tRNA
S-adenosyl-L-methionine + carboxymethylaminomethyl 2-thiouridine34 in tRNAGlu
S-adenosyl-L-homocysteine + methylaminomethyl 2-thiouridine34 in tRNAGlu + hydroxyacetate
-
-
-
-
?
S-adenosyl-L-methionine + carboxymethylaminomethyl 2-thiouridine34 in tRNAGlu
S-adenosyl-L-homocysteine + methylaminomethyl 2-thiouridine34 in tRNAGlu + hydroxyacetate
-
-
-
?
S-adenosyl-L-methionine + carboxymethylaminomethyl 2-thiouridine34 in tRNAGlu
S-adenosyl-L-homocysteine + methylaminomethyl 2-thiouridine34 in tRNAGlu + hydroxyacetate
-
-
-
?
S-adenosyl-L-methionine + carboxymethylaminomethyl 2-thiouridine34 in tRNALys
S-adenosyl-L-homocysteine + methylaminomethyl 2-thiouridine34 in tRNALys + hydroxyacetate
-
-
-
-
?
S-adenosyl-L-methionine + carboxymethylaminomethyl 2-thiouridine34 in tRNALys
S-adenosyl-L-homocysteine + methylaminomethyl 2-thiouridine34 in tRNALys + hydroxyacetate
-
-
-
?
S-adenosyl-L-methionine + carboxymethylaminomethyl 2-thiouridine34 in tRNALys
S-adenosyl-L-homocysteine + methylaminomethyl 2-thiouridine34 in tRNALys + hydroxyacetate
-
-
-
?
S-adenosyl-L-methionine + carboxymethylaminomethyl uridine34 in tRNAArg
S-adenosyl-L-homocysteine + methylaminomethyl uridine34 in tRNAArg + hydroxyacetate
-
-
-
-
?
S-adenosyl-L-methionine + carboxymethylaminomethyl uridine34 in tRNAArg
S-adenosyl-L-homocysteine + methylaminomethyl uridine34 in tRNAArg + hydroxyacetate
-
-
-
?
S-adenosyl-L-methionine + carboxymethylaminomethyl uridine34 in tRNAArg
S-adenosyl-L-homocysteine + methylaminomethyl uridine34 in tRNAArg + hydroxyacetate
-
-
-
?
S-adenosyl-L-methionine + carboxymethyluridine34 in tRNA
S-adenosyl-L-homocysteine + 5-(2-methoxy-2-oxoethyl)uridine34 in tRNA
-
-
-
?
S-adenosyl-L-methionine + carboxymethyluridine34 in tRNA
S-adenosyl-L-homocysteine + 5-(2-methoxy-2-oxoethyl)uridine34 in tRNA
the enzyme catalyzes tRNA methylation to generate 5-methylcarboxymethyl uridine at the wobble position of certain tRNAs, a critical anticodon loop modification linked to DNA damage survival
-
-
?
S-adenosyl-L-methionine + carboxymethyluridine34 in tRNA
S-adenosyl-L-homocysteine + 5-(2-methoxy-2-oxoethyl)uridine34 in tRNA
-
-
-
-
?
S-adenosyl-L-methionine + carboxymethyluridine34 in tRNA
S-adenosyl-L-homocysteine + 5-(2-methoxy-2-oxoethyl)uridine34 in tRNA
Trm9 methylates the uridine wobble base of tRNAArg(UCU) and tRNAGlU(UUC)
-
-
?
S-adenosyl-L-methionine + carboxymethyluridine34 in tRNA
S-adenosyl-L-homocysteine + 5-(2-methoxy-2-oxoethyl)uridine34 in tRNA
-
Trm9-Trm112, subunit Trm112 is required for the activity, but role of Sc Trm112 in the complex is not for catalysis
-
-
?
additional information
?
-
the bifunctional enzyme MnmC catalyzes the two consecutive reactions that convert 5-carboxymethylaminomethyl uridine to 5-methylaminomethyl uridine. The C-terminal domain of MnmC is responsible for the FAD-dependent deacetylation of cmnm5U to 5-aminomethyl uridine, whereas the N-terminal domain catalyzes the subsequent S-adenosyl-L-methionine-dependent methylation of 5-aminomethyl uridine, leading to the final product, 5-methylaminomethyl uridine, coordination of the two consecutive reactions, overview
-
-
?
additional information
?
-
-
methylaminomethyl modification of uridine or 2-thiouridine (mnm5U34 or mnm5s2U34) at the wobble position of tRNAs specific for glutamate, lysine and arginine are observed in Escherichia coli and allow for specific recognition of codons ending in A or G. In the biosynthetic pathway responsible for this posttranscriptional modification, the bifunctional enzyme MnmC catalyzes the conversion of its hypermodified substrate carboxymethylaminomethyl uridine (cmnm5U34) to mnm5U34. MnmC catalyzes the FAD-dependent oxidative cleavage of carboxymethyl group from cmnm5U34 via an imine intermediate to generate aminomethyl uridine (nm5U34), which is subsequently methylated by S-adenosyl-L-methionine to yield methylaminomethyl uridine (mnm5U34)
-
-
?
additional information
?
-
-
alternative mechanisms in formation of the 5-carboxymethyluridine34 side chain at wobble position, overview
-
-
?
additional information
?
-
methylaminomethyl modification of uridine or 2-thiouridine (mnm5U34 or mnm5s2U34) at the wobble position of tRNAs specific for glutamate, lysine and arginine are observed in Escherichia coli and allow for specific recognition of codons ending in A or G. In the biosynthetic pathway responsible for this posttranscriptional modification, the bifunctional enzyme MnmC catalyzes the conversion of its hypermodified substrate carboxymethylaminomethyl uridine (cmnm5U34) to mnm5U34. MnmC catalyzes the FAD-dependent oxidative cleavage of carboxymethyl group from cmnm5U34 via an imine intermediate to generate aminomethyl uridine (nm5U34), which is subsequently methylated by S-adenosyl-L-methionine to yield methylaminomethyl uridine (mnm5U34)
-
-
?
additional information
?
-
methylaminomethyl modification of uridine or 2-thiouridine (mnm5U34 or mnm5s2U34) at the wobble position of tRNAs specific for glutamate, lysine and arginine are observed in Escherichia coli and allow for specific recognition of codons ending in A or G. In the biosynthetic pathway responsible for this posttranscriptional modification, the bifunctional enzyme MnmC catalyzes the conversion of its hypermodified substrate carboxymethylaminomethyl uridine (cmnm5U34) to mnm5U34. MnmC catalyzes the FAD-dependent oxidative cleavage of carboxymethyl group from cmnm5U34 via an imine intermediate to generate aminomethyl uridine (nm5U34), which is subsequently methylated by S-adenosyl-L-methionine to yield methylaminomethyl uridine (mnm5U34)
-
-
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
S-adenosyl-S-carboxymethyl-L-homocysteine
i.e. [(3S)-3-amino-3-carboxypropyl]{[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl}(carboxymethyl)sulfanium, the enzyme contains a cofactor, S-adenosyl-S-carboxymethyl-L-homocysteine (SCM-SAH), in which the donor methyl group is substituted by a carboxymethyl group. The carboxyl moiety forms a salt-bridge interaction with Arg199 that is conserved in a large group of CmoA-related proteins but is not conserved in other S-adenosyl-L-methionine-containing enzymes. The active site contains one molecule cofactor S-adenosyl-S-carboxymethyl-L-homocysteine per monomer, and not S-adenosyl-L-methionine
FAD
-
required for oxidative cleavage of carboxymethyl group from cmnm5U34, FAD-binding site structure, overview
FAD
required for oxidative cleavage of carboxymethyl group from cmnm5U34, FAD-binding site structure, overview
S-adenosyl-L-methionine
-
dependent on, the N-terminal MnmC2 domain is composed of residues 1-245 and contains the SAM binding site. The binding pocket is composed of mostly hydrophobic residues, except for Glu101 and Asp178
S-adenosyl-L-methionine
dependent on, the N-terminal MnmC2 domain is composed of residues 1-245 and contains the SAM binding site. The binding pocket is composed of mostly hydrophobic residues, except for Glu101 and Asp178
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TRM112
interaction of ALKBH8 with a small accessory protein, TRM112, is required to form a functional tRNA methyltransferase
-
Trm112 p
-
the presence of Trm112p dramatically improves the methyltransferase activity of Trm9p in vitro
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Trm112p
when produced in Escherichia coli, Trm112p forms a complex with Trm9p, which renders the latter soluble. This recombinant complex catalyzes the formation of mcm5U34 (5-methoxycarbonylmethyluridine) on tRNA in vitro but not mcm5s2U34 (5-methoxycarbonylmethyl-2-thiouridine)
-
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
evolution
-
comparison of the MnmC2 active sites between Escherichia coli MnmC and Yersinia pestis MnmC, overview. Structural comparison with MnmC2 of Aquifex aeolicus
evolution
comparison of the MnmC2 active sites between Escherichia coli MnmC and Yersinia pestis MnmC, overview. Structural comparison with MnmC2 of Aquifex aeolicus
evolution
conservation of Arg199, the key residue of CmoA that stabilizes the negative charge of the carboxyl group of the S-adenosyl-S-carboxymethyl-L-homocysteine cofactor, suggests that these proteins contain the S-adenosyl-S-carboxymethyl-L-homocysteine cofactor instead of S-adenosyl-L-methionine. The equivalent residue in known S-adenosyl-L-methionine-dependent methyltransferases is not conserved
evolution
-
the mcm5U family of modifications is found only in eukaryotes and is implicated in efficient reading of AGA and AAG codons by tRNAArg (UCU) and tRNAGlu(UUC), respectively in Saccharomyyces cerevisiae. Trm112 partners with several methyltransferases involved in diverse translational processes and has distinct roles in other methyltransferase complexes
evolution
-
comparison of the MnmC2 active sites between Escherichia coli MnmC and Yersinia pestis MnmC, overview. Structural comparison with MnmC2 of Aquifex aeolicus
-
malfunction
ABH8 depletion in human cells reduces endogenous levels of 5-methoxycarboxymethyluridine in RNA and increases cellular sensitivity to DNA-damaging agents
malfunction
in intact yeast cells, disruption of the TRM9 gene results in the complete loss of the modified wobble bases (5-methylcarbonylmethyluridine in tRNAArg3 and 5-methylcarbonylmethyl-2-thiouridine in tRNAGlu) and increased sensitivity at 37°C to paromomycin, a translational inhibitor. trm9-deletion mutants are hypersensitive to the translational inhibitor paromomycin at elevated temperatures, suggesting the importance of the methyl-esterified bases during heat shock
malfunction
mcm5U, mcm5Um, and mcm5s2U are detected in total tRNA from wild-type livers but are completely absent from total tRNA from Alkbh8-/- mice. Substantial amounts of cm5U, the putative unmethylated precursor of mcm5U, is detected in total tRNA from Alkbh8-/- mice but not in total tRNA from wild-type mice. Despite the complete loss of all of these uridine modifications, Alkbh8-/- mice appear normal. However, the selenocysteine-specific tRNA is aberrantly modified in the Alkbh8-/- mice, and for the selenoprotein Gpx1, a reduced recoding of the UGA stop codon to selenocysteine is observed
malfunction
silencing of ALKBH8 through small interfering RNA transfection reduced reactive oxygen species (ROS) production via down-regulation of NAD(P)H oxidase-1 (NOX-1) and induced apoptosis through subsequent activation of c-jun NH2-terminal kinase (JNK) and p38. Silencing of ALKBH8 significantly suppresses invasion, angiogenesis, and growth of bladder cancers in vivo
malfunction
trm9DELTA cells lacking a tRNA methylase specific for wobble uridine (U34) residues survive zymocin
malfunction
-
5-methoxycarbonylmethyl-uridine or 5-methoxycarbonylmethyl-2-thiouridine are absent in tRNAs in trm9DELTA or trm112DELTA mutants, while intermediates 5-carbamoylmethyluridine and 5-methoxycarbonylmethyl-2-thiouridine are accumulating
malfunction
-
Trm9DELTA mutation causes lack of the 5-methoxycarbonylmethyluridine (mcm5U34) modification in yeast which is associated with sensitivity to DNA damaging agents as well as with sensitivity to aminoglycosides at high temperature and resistance to zymocin-mediated tRNA cleavage and cell death. Mutants encoding Sc Trm9 variants lacking the C-terminal domain required for interaction with Sc Trm112 act as suppressors of zymocin toxicity
metabolism
-
Trm9p and Trm112p function together at the final step in formation of 5-methoxycarbonylmethyl-uridine in tRNA by using the intermediate 5-carbamoylmethyluridine as a substrate
metabolism
-
MnmC (formally known as YfcK or TrmC) is a bifunctional enzyme responsible for the final two steps of biosynthetic pathway of mnm5s2U in tRNAGlu and tRNALys, and mnm5U in tRNAArg
metabolism
MnmC (formally known as YfcK or TrmC) is a bifunctional enzyme responsible for the final two steps of biosynthetic pathway of mnm5s2U in tRNAGlu and tRNALys, and mnm5U in tRNAArg
metabolism
-
MnmC (formally known as YfcK or TrmC) is a bifunctional enzyme responsible for the final two steps of biosynthetic pathway of mnm5s2U in tRNAGlu and tRNALys, and mnm5U in tRNAArg
-
physiological function
ALKBH8 is an upstream target of NOX-1 and is involved in intracellular ROS generation. ALKBH8/NOX-1 signals function mainly in the acquisition of the aggressive human urothelial carcinoma phenotype
physiological function
ALKBH8-mediated methylation is a prerequisite for the thiolation and 2'-O-ribose methylation that form 5-methoxycarbonylmethyl-2-thiouridine and 5-methoxycarbonylmethyl-2'-O-methyluridine, respectively
physiological function
required for wobble uridine modification and DNA damage survival
physiological function
Trm9 prevents cell death via translational enhancement of DNA damage response proteins. Trm9-specific tRNA modifications enhance codon-specific translation elongation and promote increased levels of key damage response proteins
physiological function
-
at position 34, the majority of yeast cytosolic tRNA species that have a uridine are modified to 5-carbamoylmethyluridine, 5-carbamoylmethyl-2'-O-methyluridine, 5-methoxycarbonylmethyl-uridine or 5-methoxycarbonylmethyl-2-thiouridine. The formation of 5-methoxycarbonylmethyl-uridine and 5-carbamoylmethyluridine side chains involves a complex pathway, where the last step in formation of mcm5 is a methyl esterification of 5-carboxymethyl dependent on the Trm9 and Trm112 proteins. Both Trm9 and Trm112 are required for the last step in formation of 5-methoxycarbonylmethyl side chains at wobble uridines
physiological function
posttranscriptional modifications of bases within the tRNA anticodon significantly affect the decoding system, uridines at the wobble position U34 of some tRNAs are modified to 5-methyluridine derivatives. These xm5U34-containing tRNAs read codons ending with A or G, whereas tRNAs with the unmodified U34 are able to read all four synonymous codons of a family box
physiological function
uridine at position 34 of bacterial transfer RNAs is commonly modified to uridine-5-oxyacetic acid (cmo5U) to increase the decoding capacity. The protein CmoA is involved in the formation of cmo5U
additional information
-
crystal structure of MnmC from the Gram negative bacterium reveals the overall architecture of the enzyme and the relative disposition of the two independent catalytic domains: a Rossmann-fold domain containing the S-adenosyl-L-methionine binding site and an FAD containing domain structurally homologous to glycine oxidase from Bacillus subtilis. The structure of MnmC also reveals the detailed atomic interactions at the interdomain interface and provide spatial restraints relevant to the overall catalytic mechanism
additional information
crystal structures of MnmC from two Gram negative bacteria reveal the overall architecture of the enzyme and the relative disposition of the two independent catalytic domains: a Rossmann-fold domain containing the S-adenosyl-L-methionine binding site and an FAD containing domain structurally homologous to glycine oxidase from Bacillus subtilis. The structures of MnmC also reveal the detailed atomic interactions at the interdomain interface and provide spatial restraints relevant to the overall catalytic mechanism
additional information
-
different catalytic subunits, e.g. Trm9, engage the same partner protein Trm112 to direct different chemical modifications on different residues
additional information
-
crystal structures of MnmC from two Gram negative bacteria reveal the overall architecture of the enzyme and the relative disposition of the two independent catalytic domains: a Rossmann-fold domain containing the S-adenosyl-L-methionine binding site and an FAD containing domain structurally homologous to glycine oxidase from Bacillus subtilis. The structures of MnmC also reveal the detailed atomic interactions at the interdomain interface and provide spatial restraints relevant to the overall catalytic mechanism
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Show AA Sequence and Transmembrane Helices (929 entries)
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
55600
2 x 52500, gel filtration, mass spectrometry, and crystal structure analysis, 2 * 55600, about, sequence calculation. There are two molecules of CmoA present in the asymmetric unit, both molecules of CmoA contain the novel derivative S-adenosyl-S-carboxymethyl-L-homocysteine, the two molecules adopt the same conformation
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
2 x 52500, gel filtration, mass spectrometry, and crystal structure analysis, 2 * 55600, about, sequence calculation. There are two molecules of CmoA present in the asymmetric unit, both molecules of CmoA contain the novel derivative S-adenosyl-S-carboxymethyl-L-homocysteine, the two molecules adopt the same conformation
heterodimer
-
the enzyme is formed by catalytic subunit Trm9 and regulatory subunit Trm112
monomer
additional information
additional information
methyltransferase domain MnmC2 domain adopts the canonical class I methyltransferase fold
additional information
ALKBH8 and TRM112 form a functional tRNA methyltransferase complex (Trm112 is an accessory protein required for several methyltransferases)
additional information
-
different catalytic subunits engage the same partner protein Trm112 to direct different chemical modifications on different residues
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified enzyme in complex with cofactors S-adenosyl-L-methionine and FAD, sitting drop vapor diffusion method, 21°C, by mixing 0.001 ml of 10 mg/ml protein with 0.001 ml of reservoir solution containing 1.8 M tri-ammonium citrate, pH 7.0 and 0.5% ethyl acetate, X-ray diffraction structure determination and analysis at 2.3 A resolution
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purified MnmC containing FAD, sitting drop method, the optimal reservoir solution contains 100 mM Bis-Tris, pH 5.5, containing 25% w/v PEG3350, 250 mM ammonium sulfate, and 10 mM hexamine cobalt(III) chloride, 5 days, X-ray diffraction structure determination and analysis at 3.0 A resolution
purified recombinant detagged enzyme, sitting drop vapour diffusion method, mixing of 100 nl of 20 mg/ml protein in 200 mM NaCl, and 20 mM Tris, pH 7.5, with 100 nl of precipitation solution containing 0.3 M diethylene glycol, 0.3 M triethylene glycol, 0.3 M tetraethylene glycol, 0.3 M pentaethylene glycol, 0.1 M MOPS/HEPES-Na, pH 7.5, 12.5% w/v PEG 1000, 12.5% w/v PEG 3350, 12.5% w/v MPD, 5 h, X-ray diffraction structure determination and analysis at 1.73 A resolution, molecular replacement using the structure of Haemophilus influenzae YecO, PDB ID 1im8, chain B
purified enzyme in complex with cofactors S-adenosyl-L-methionine and FAD or in complex with FAD alone, sitting drop vapor diffusion method, 21°C, by mixing 0.001 ml of 10 mg/ml protein with 0.001 ml of reservoir solution containing 0.1 M HEPES, pH 7.0, and 30% v/v Jeffamine ED-2001 reagent, X-ray diffraction structure determination and analysis at 2.3 A resolution
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
co-purification of His-tagged Trm9p with untagged Trm112p as a complex from Escherichia coli strain BL21(DE3)pLysS by nickel affinity chromatography
-
recombinant His-tagged enzyme from Escherichia coli strain Rosetta pLysS (DE3) by nickel affinity chromatography and gel filtration, followed by cleavage of the N-terminal His6-tag with rhinovirus 3C protease and another step of nickel affinity chromatography to remove the tag
recombinant N-terminally His6-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, tag cleavage with thrombin , and again nickel adffinity chromatography for tag removal, followed by gel filtration
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recombinant N-terminally His6-tagged wild-type and selenomethionine-labeled enzyme from Escherichia coli strains by nickel affinity chromatography, tag cleavage with enterokinase, and again nickel adffinity chromatography for tag removal, followed by gel filtration
recombinant wild-type and selenomethinone-labeled enzymes from Escherichia coli by ultracentrifugation, anion exchange and hydrophobic interaction chromatography, another step of anion exchange chromatography and gel filtration
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
co-expression of His-tagged Trm9p with untagged Trm112p in Escherichia coli strain BL21(DE3)pLysS, Trm9p/Trm112p complex formation
-
expression of GST-Trm9 fusion protein in Escherichia coli DH5alpha cells
gene cmoA, recombinant expression of N-terminally His-tagged enzyme in Escherichia coli strain Rosetta pLysS (DE3)
gene JW5380, expression of wild-type and selenomethinone-labeled MnmC in Escherichia coli strains Rosetta2(DE3) and B834(DE3), respectively
gene mnmC, recombinant expression of N-terminally His6-tagged enzyme in Escherichia coli strain BL21(DE3)
-
gene mnmC, recombinant expression of N-terminally His6-tagged enzyme in Escherichia coli strain BL21(DE3), expression of selenomethionine-labeled enzyme in Escherichia coli strain B834
the FLAG-tagged-ABH8 coding region is cloned into the pBABEpuro or pBABEhygro retroviral vector. HeLa S3 cells are infected with retrovirus
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
DNA-damaging agents induce ABH8 expression in an ATM(central DNA damage kinase)-dependent manner
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
transurethral injection of ALKBH8 small interfering RNA (siRNA) offers promise as a new therapeutic strategy for bladder cancer
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kalhor, H.R.; Clarke, S.
Novel methyltransferase for modified uridine residues at the wobble position of tRNA
Mol. Cell. Biol.
23
9283-9292
2003
Saccharomyces cerevisiae (P49957), Saccharomyces cerevisiae
brenda
Shimada, K.; Nakamura, M.; Anai, S.; de Velasco, M.; Tanaka, M.; Tsujikawa, K.; Ouji, Y.; Konishi, N.
A novel human AlkB homologue, ALKBH8, contributes to human bladder cancer progression
Cancer Res.
69
3157-3164
2009
Homo sapiens (Q96BT7)
brenda
Mazauric, M.H.; Dirick, L.; Purushothaman, S.K.; Bjrk, G.R.; Lapeyre, B.
Trm112p is a 15-kDa zinc finger protein essential for the activity of two tRNA and one protein methyltransferases in yeast
J. Biol. Chem.
285
18505-18515
2010
Saccharomyces cerevisiae (P49957), Saccharomyces cerevisiae
brenda
Songe-Moller, L.; van den Born, E.; Leihne, V.; Vagbo C.B.; Kristoffersen, T.; Krokan, H.E.; Kirpekar, F.; Falnes, P.O.; Klungland, A.
Mammalian ALKBH8 possesses tRNA methyltransferase activity required for the biogenesis of multiple wobble uridine modifications implicated in translational decoding
Mol. Cell. Biol.
30
1814-1827
2010
Mus musculus (Q80Y20)
brenda
Fu, D.; Brophy, J.A.; Chan, C.T.; Atmore, K.A.; Begley, U.; Paules, R.S.; Dedon, P.C.; Begley, T.J.; Samson, L.D.
Human AlkB homolog ABH8 is a tRNA methyltransferase required for wobble uridine modification and DNA damage survival
Mol. Cell. Biol.
30
2449-2459
2010
Homo sapiens (Q96BT7)
brenda
Begley, U.; Dyavaiah, M.; Patil, A.; Rooney, J.P.; DiRenzo, D.; Young, C.M.; Conklin, D.S.; Zitomer, R.S.; Begley, T.J.
Trm9-catalyzed tRNA modifications link translation to the DNA damage response
Mol. Cell
28
860-870
2007
Saccharomyces cerevisiae (P49957), Saccharomyces cerevisiae
brenda
Jablonowski, D.; Zink, S.; Mehlgarten, C.; Daum, G.; Schaffrath, R.
tRNAGlu wobble uridine methylation by Trm9 identifies Elongator's key role for zymocin-induced cell death in yeast
Mol. Microbiol.
59
677-688
2006
Saccharomyces cerevisiae (P49957)
brenda
Chen, C.; Huang, B.; Anderson, J.T.; Bystroem, A.S.
Unexpected accumulation of ncm5U and ncm5S2U in a trm9 mutant suggests an additional step in the synthesis of mcm5U and mcm5S2U
PLoS ONE
6
e20783
2011
Saccharomyces cerevisiae
brenda
Kitamura, A.; Sengoku, T.; Nishimoto, M.; Yokoyama, S.; Bessho, Y.
Crystal structure of the bifunctional tRNA modification enzyme MnmC from Escherichia coli
Protein Sci.
20
1105-1113
2011
Escherichia coli (P77182)
brenda
Byrne, R.T.; Whelan, F.; Aller, P.; Bird, L.E.; Dowle, A.; Lobley, C.M.; Reddivari, Y.; Nettleship, J.E.; Owens, R.J.; Antson, A.A.; Waterman, D.G.
S-Adenosyl-S-carboxymethyl-L-homocysteine: a novel cofactor found in the putative tRNA-modifying enzyme CmoA
Acta Crystallogr. Sect. D
69
1090-1098
2013
Escherichia coli (P76290)
brenda
Kim, J.; Almo, S.C.
Structural basis for hypermodification of the wobble uridine in tRNA by bifunctional enzyme MnmC
BMC Struct. Biol.
13
5
2013
Escherichia coli
brenda
Kim, J.; Almo, S.C.
Structural basis for hypermodification of the wobble uridine in tRNA by bifunctional enzyme MnmC
BMC Struct. Biol.
13
5-5
2013
Yersinia pestis (Q8ZD36), Yersinia pestis Kim (Q8ZD36)
brenda
Guy, M.P.; Phizicky, E.M.
Two-subunit enzymes involved in eukaryotic post-transcriptional tRNA modification
RNA Biol.
11
1608-1618
2014
Saccharomyces cerevisiae
brenda
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