2.1.1.229: tRNA (carboxymethyluridine34-5-O)-methyltransferase
This is an abbreviated version!
For detailed information about tRNA (carboxymethyluridine34-5-O)-methyltransferase, go to the full flat file.
Word Map on EC 2.1.1.229
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2.1.1.229
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wobble
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methyltransferases
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5-methoxycarbonylmethyluridine
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ribonucleotide
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anticodon
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gene-specific
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trnagluuuc
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translationally
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medicine
- 2.1.1.229
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wobble
- methyltransferases
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5-methoxycarbonylmethyluridine
- ribonucleotide
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anticodon
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gene-specific
- trnagluuuc
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translationally
- medicine
Reaction
Synonyms
ABH8, ALKBH8, CmoA, MnmC, Trm9, Trm9-Trm112, Trm9p, TrmC, tRNA methyltransferase 9, YfcK, YML014w
ECTree
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General Information
General Information on EC 2.1.1.229 - tRNA (carboxymethyluridine34-5-O)-methyltransferase
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evolution
malfunction
metabolism
physiological function
additional information
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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
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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
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comparison of the MnmC2 active sites between Escherichia coli MnmC and Yersinia pestis MnmC, overview. Structural comparison with MnmC2 of Aquifex aeolicus
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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
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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
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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
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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
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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
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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
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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
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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
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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
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different catalytic subunits, e.g. Trm9, engage the same partner protein Trm112 to direct different chemical modifications on different residues
additional information
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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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