Rhea - reaction knowledgebase

Enzymes

UniProtKB ^help_outline	750 proteins
Enzyme class ^help_outline	EC 2.1.1.229 tRNA (carboxymethyluridine(34)-5-O)-methyltransferase
GO Molecular Function ^help_outline	GO:0106335 tRNA (5-carboxymethyluridine(34)-5-O)-methyltransferase activity

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Name^help_outline 5-(carboxymethyl)uridine³⁴ in tRNA Identifier RHEA-COMP:10407 Reactive part ^help_outline
- Name ^help_outline carboxymethyluridine 5'-phosphate residue Identifier CHEBI:74882 Charge -2 Formula C11H11N2O10P Position^help_outline 34 SMILES^help_outline C1=C(C(NC(N1[C@@H]2O[C@H](COP(*)(=O)[O-])[C@H]([C@H]2O)O*)=O)=O)CC([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 2 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Search links Involved in 2 reaction(s) Find proteins in UniProtKB for this molecule
Name ^help_outline S-adenosyl-L-methionine Identifier CHEBI:59789 Charge 1 Formula C15H23N6O5S InChIKey^help_outline MEFKEPWMEQBLKI-AIRLBKTGSA-O SMILES^help_outline C[S+](CC[C@H]([NH3+])C([O-])=O)C[C@H]1O[C@H]([C@H](O)[C@@H]1O)n1cnc2c(N)ncnc12 2D coordinates Mol file for the small molecule Search links Involved in 842 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Name^help_outline 5-(2-methoxy-2-oxoethyl)uridine³⁴ in tRNA Identifier RHEA-COMP:10408 Reactive part ^help_outline
- Name ^help_outline 5-(2-methoxy-2-oxoethyl)uridine 5'-phosphate residue Identifier CHEBI:74851 Charge -1 Formula C12H14N2O10P Position^help_outline 34 SMILES^help_outline C1=C(C(NC(N1[C@@H]2O[C@H](COP(*)(=O)[O-])[C@H]([C@H]2O)O*)=O)=O)CC(OC)=O 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Search links Involved in 1 reaction(s) Find proteins in UniProtKB for this molecule
Name ^help_outline S-adenosyl-L-homocysteine Identifier CHEBI:57856 Charge 0 Formula C14H20N6O5S InChIKey^help_outline ZJUKTBDSGOFHSH-WFMPWKQPSA-N SMILES^help_outline Nc1ncnc2n(cnc12)[C@@H]1O[C@H](CSCC[C@H]([NH3+])C([O-])=O)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 768 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule

Cross-references

	RHEA:43208	RHEA:43209	RHEA:43210	RHEA:43211
Reaction direction	undefined	left-to-right	right-to-left	bidirectional
UniProtKB ^help_outline	750 proteins
EC numbers ^help_outline	2.1.1.229
Gene Ontology ^help_outline	GO:0106335
MetaCyc ^help_outline		RXN-12461

Publications

Human AlkB homolog ABH8 is a tRNA methyltransferase required for wobble uridine modification and DNA damage survival.

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.

tRNA nucleosides are extensively modified to ensure their proper function in translation. However, many of the enzymes responsible for tRNA modifications in mammals await identification. Here, we show that human AlkB homolog 8 (ABH8) catalyzes tRNA methylation to generate 5-methylcarboxymethyl uri ... >> More

tRNA nucleosides are extensively modified to ensure their proper function in translation. However, many of the enzymes responsible for tRNA modifications in mammals await identification. Here, we show that human AlkB homolog 8 (ABH8) catalyzes tRNA methylation to generate 5-methylcarboxymethyl uridine (mcm(5)U) at the wobble position of certain tRNAs, a critical anticodon loop modification linked to DNA damage survival. We find that ABH8 interacts specifically with tRNAs containing mcm(5)U and that purified ABH8 complexes methylate RNA in vitro. Significantly, ABH8 depletion in human cells reduces endogenous levels of mcm(5)U in RNA and increases cellular sensitivity to DNA-damaging agents. Moreover, DNA-damaging agents induce ABH8 expression in an ATM-dependent manner. These results expand the role of mammalian AlkB proteins beyond that of direct DNA repair and support a regulatory mechanism in the DNA damage response pathway involving modulation of tRNA modification. << Less

Mol. Cell. Biol. 30:2449-2459(2010) [PubMed] [EuropePMC]
Novel methyltransferase for modified uridine residues at the wobble position of tRNA.

Kalhor H.R., Clarke S.

We have identified a novel tRNA methyltransferase in Saccharomyces cerevisiae that we designate Trm9. This enzyme, the product of the YML014w gene, catalyzes the esterification of modified uridine nucleotides, resulting in the formation of 5-methylcarbonylmethyluridine in tRNA(Arg3) and 5-methylca ... >> More

We have identified a novel tRNA methyltransferase in Saccharomyces cerevisiae that we designate Trm9. This enzyme, the product of the YML014w gene, catalyzes the esterification of modified uridine nucleotides, resulting in the formation of 5-methylcarbonylmethyluridine in tRNA(Arg3) and 5-methylcarbonylmethyl-2-thiouridine in tRNA(Glu). In intact yeast cells, disruption of the TRM9 gene results in the complete loss of these modified wobble bases and increased sensitivity at 37 degrees C to paromomycin, a translational inhibitor. These results suggest a role for this potentially reversible methyl esterification reaction when cells are under stress. << Less

Mol. Cell. Biol. 23:9283-9292(2003) [PubMed] [EuropePMC]
Mammalian ALKBH8 possesses tRNA methyltransferase activity required for the biogenesis of multiple wobble uridine modifications implicated in translational decoding.

Songe-Moller L., van den Born E., Leihne V., Vagbo C.B., Kristoffersen T., Krokan H.E., Kirpekar F., Falnes P.O., Klungland A.

Uridines in the wobble position of tRNA are almost invariably modified. Modifications can increase the efficiency of codon reading, but they also prevent mistranslation by limiting wobbling. In mammals, several tRNAs have 5-methoxycarbonylmethyluridine (mcm5U) or derivatives thereof in the wobble ... >> More

Uridines in the wobble position of tRNA are almost invariably modified. Modifications can increase the efficiency of codon reading, but they also prevent mistranslation by limiting wobbling. In mammals, several tRNAs have 5-methoxycarbonylmethyluridine (mcm5U) or derivatives thereof in the wobble position. Through analysis of tRNA from Alkbh8-/-mice, we show here that ALKBH8 is a tRNA methyltransferase required for the final step in the biogenesis of mcm5U. We also demonstrate that the interaction of ALKBH8 with a small accessory protein, TRM112, is required to form a functional tRNA methyltransferase. Furthermore, prior ALKBH8-mediated methylation is a prerequisite for the thiolation and 2'-O-ribose methylation that form 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U) and 5-methoxycarbonylmethyl-2'-O-methyluridine (mcm5Um), respectively. Despite the complete loss of all of these uridine modifications, Alkbh8-/-mice appear normal. However, the selenocysteine-specific tRNA (tRNASec) is aberrantly modified in the Alkbh8-/-mice, and for the selenoprotein Gpx1, we indeed observed reduced recoding of the UGA stop codon to selenocysteine. << Less

Mol. Cell. Biol. 30:1814-1827(2010) [PubMed] [EuropePMC]

RHEA:43208 5-(carboxymethyl)uridine(34) in tRNA + S-adenosyl-L-methionine = 5-(2-methoxy-2-oxoethyl)uridine(34) in tRNA + S-adenosyl-L-homocysteine

Enzymes

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Cross-references

Publications

Human AlkB homolog ABH8 is a tRNA methyltransferase required for wobble uridine modification and DNA damage survival.

Novel methyltransferase for modified uridine residues at the wobble position of tRNA.

Mammalian ALKBH8 possesses tRNA methyltransferase activity required for the biogenesis of multiple wobble uridine modifications implicated in translational decoding.