Synthesis of wybutosine at G37 of tRNA(Phe) (Homo sapiens)
From WikiPathways
Description
Derivatives of wyosine are tricyclic bases found at nucleotide 37 of tRNA(Phe) in eukaryotes. The pathway of wybutosine synthesis begins with a templated guanosine residue and proceeds through 6 steps catalyzed by 5 enzymes: N1 methylation of guanosine, condensation of 1-methylguanosine with pyruvate to yield 4-demethylwyosine, addition of an aminocarboxypropyl group to yield yW-86, methylation of yW-86 to yield yW-72, methylation of yW-72 to yield yW-58, and methoxycarbonylation of yW-58 to yield wybutosine (reviewed in Young and Bandarian 2013, Perche-Letuvée et al. 2014). Wybutosine may further be modified by hydroxylation and methylation. Wyosine derivatives at position 37 of tRNAs participate in translational fidelity by stabilizing codon-anticodon pairing (Konevega et al. 2004) and preventing frameshifting (Waas et al. 2007).
View original pathway at:Reactome.
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Ontology Terms
Saving...Bibliography
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- Perche-Letuvée P, Molle T, Forouhar F, Mulliez E, Atta M.; ''Wybutosine biosynthesis: structural and mechanistic overview.''; PubMed Europe PMC Scholia
- Kato M, Araiso Y, Noma A, Nagao A, Suzuki T, Ishitani R, Nureki O.; ''Crystal structure of a novel JmjC-domain-containing protein, TYW5, involved in tRNA modification.''; PubMed Europe PMC Scholia
- Noma A, Ishitani R, Kato M, Nagao A, Nureki O, Suzuki T.; ''Expanding role of the jumonji C domain as an RNA hydroxylase.''; PubMed Europe PMC Scholia
- Rodriguez V, Vasudevan S, Noma A, Carlson BA, Green JE, Suzuki T, Chandrasekharappa SC.; ''Structure-function analysis of human TYW2 enzyme required for the biosynthesis of a highly modified Wybutosine (yW) base in phenylalanine-tRNA.''; PubMed Europe PMC Scholia
- Waas WF, Druzina Z, Hanan M, Schimmel P.; ''Role of a tRNA base modification and its precursors in frameshifting in eukaryotes.''; PubMed Europe PMC Scholia
- Christian T, Gamper H, Hou YM.; ''Conservation of structure and mechanism by Trm5 enzymes.''; PubMed Europe PMC Scholia
- Brulé H, Elliott M, Redlak M, Zehner ZE, Holmes WM.; ''Isolation and characterization of the human tRNA-(N1G37) methyltransferase (TRM5) and comparison to the Escherichia coli TrmD protein.''; PubMed Europe PMC Scholia
- Young AP, Bandarian V.; ''Radical mediated ring formation in the biosynthesis of the hypermodified tRNA base wybutosine.''; PubMed Europe PMC Scholia
- Konevega AL, Soboleva NG, Makhno VI, Semenkov YP, Wintermeyer W, Rodnina MV, Katunin VI.; ''Purine bases at position 37 of tRNA stabilize codon-anticodon interaction in the ribosomal A site by stacking and Mg2+-dependent interactions.''; PubMed Europe PMC Scholia
History
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External references
DataNodes
| View all... |
| Name | Type | Database reference | Comment |
|---|---|---|---|
| 2OG | Metabolite | CHEBI:16810 (ChEBI)  | |
| 4Fe-4S cluster | Metabolite | CHEBI:49883 (ChEBI) | |
| 5'-deoxyadenosine | Metabolite | CHEBI:17319 (ChEBI) | |
| AdoHcy | Metabolite | CHEBI:16680 (ChEBI) | |
| AdoMet | Metabolite | CHEBI:15414 (ChEBI) | |
| CO2 | Metabolite | CHEBI:16526 (ChEBI) | |
| FMN | Metabolite | CHEBI:17621 (ChEBI) | |
| Fe2+ | Metabolite | CHEBI:18248 (ChEBI) | |
| H2O | Metabolite | CHEBI:15377 (ChEBI) | |
| L-Met | Metabolite | CHEBI:16643 (ChEBI) | |
| LCMT2 | Protein | O60294 (Uniprot-TrEMBL) | |
| MTAD | Metabolite | CHEBI:17509 (ChEBI) | |
| O2 | Metabolite | CHEBI:15379 (ChEBI) | |
| SUCCA | Metabolite | CHEBI:15741 (ChEBI) | |
| TRMT12 | Protein | Q53H54 (Uniprot-TrEMBL) | |
| TRMT5 | Protein | Q32P41 (Uniprot-TrEMBL) | |
| TYW1 | Protein | Q9NV66 (Uniprot-TrEMBL) | |
| TYW1:FMN:4Fe-4S | Complex | R-HSA-6782882 (Reactome) | |
| TYW3 | Protein | Q6IPR3 (Uniprot-TrEMBL) | |
| TYW5 | Protein | A2RUC4 (Uniprot-TrEMBL) | |
| TYW5:Fe2+ dimer | Complex | R-HSA-6783460 (Reactome) | |
| pyruvate | Metabolite | CHEBI:32816 (ChEBI) | |
| tRNA(Phe) containing 1-methylG-37 | R-HSA-6782902 (Reactome) | ||
| tRNA(Phe) containing 1-methylG-37 | R-HSA-6783390 (Reactome) | ||
| tRNA(Phe) containing G-37 | R-HSA-6782877 (Reactome) | ||
| tRNA(Phe) containing OHyW at 37 | R-HSA-6783457 (Reactome) | ||
| tRNA(Phe) containing OHyW-72 at 37 | R-HSA-6783496 (Reactome) | ||
| tRNA(Phe) containing yW at 37 | R-HSA-6782903 (Reactome) | ||
| tRNA(Phe) containing yW-187 at 37 | R-HSA-6782898 (Reactome) | ||
| tRNA(Phe) containing yW-58 at 37 | R-HSA-6782864 (Reactome) | ||
| tRNA(Phe) containing yW-72 at 37 | R-HSA-6782871 (Reactome) | ||
| tRNA(Phe) containing yW-86 at 37 | R-HSA-6782880 (Reactome) |
Annotated Interactions
| View all... |
| Source | Target | Type | Database reference | Comment |
|---|---|---|---|---|
| 2OG | R-HSA-6783455 (Reactome) | |||
| 5'-deoxyadenosine | Arrow | R-HSA-6782895 (Reactome) | ||
| AdoHcy | Arrow | R-HSA-6782859 (Reactome) | ||
| AdoHcy | Arrow | R-HSA-6782879 (Reactome) | ||
| AdoHcy | Arrow | R-HSA-6782881 (Reactome) | ||
| AdoHcy | Arrow | R-HSA-6782890 (Reactome) | ||
| AdoHcy | Arrow | R-HSA-6783473 (Reactome) | ||
| AdoMet | R-HSA-6782859 (Reactome) | |||
| AdoMet | R-HSA-6782879 (Reactome) | |||
| AdoMet | R-HSA-6782881 (Reactome) | |||
| AdoMet | R-HSA-6782890 (Reactome) | |||
| AdoMet | R-HSA-6782893 (Reactome) | |||
| AdoMet | R-HSA-6782895 (Reactome) | |||
| AdoMet | R-HSA-6783473 (Reactome) | |||
| CO2 | Arrow | R-HSA-6782895 (Reactome) | ||
| CO2 | Arrow | R-HSA-6783455 (Reactome) | ||
| CO2 | R-HSA-6782890 (Reactome) | |||
| CO2 | R-HSA-6783473 (Reactome) | |||
| H2O | Arrow | R-HSA-6782895 (Reactome) | ||
| L-Met | Arrow | R-HSA-6782895 (Reactome) | ||
| LCMT2 | mim-catalysis | R-HSA-6782881 (Reactome) | ||
| LCMT2 | mim-catalysis | R-HSA-6782890 (Reactome) | ||
| LCMT2 | mim-catalysis | R-HSA-6783473 (Reactome) | ||
| MTAD | Arrow | R-HSA-6782893 (Reactome) | ||
| O2 | R-HSA-6783455 (Reactome) | |||
| R-HSA-6782859 (Reactome) | TRMT5 transfers a methyl group from S-adenosylmethionine to the 1 position of guanosine-37 of tRNA(Phe) (Brulé et al. 2004, Christian et al. 2013). The yeast homolog, TRM5, catalyzes the same reaction. | |||
| R-HSA-6782879 (Reactome) | As inferred from homologs in Saccharomyces cerevisiae, TYW3 transfers a methyl group from S-adenosylmethionine to yW-86 (7-((3S)-(3-amino-3-carboxypropyl))-4-demethylwyosine) at nucleotide 37 of tRNA(Phe), yielding yW-72 (7-((3S)-(3-amino-3-carboxypropyl))wyosine) and S-adenosylhomocysteine. | |||
| R-HSA-6782881 (Reactome) | As inferred from homologues in Saccharomyces cerevisiae, LCMT2 (TYW4) transfers a methyl group from S-adenosylmethionine to yW-72 (7-((3S)-3-amino-3-carboxypropyl)wyosine) at nucleotide 37 of tRNA(Phe), yielding yW-58 (7-((3S)-3-amino-3-(methoxycarbonyl)propyl)wyosine) and S-adenosylhomocysteine. | |||
| R-HSA-6782890 (Reactome) | As inferred from homologues in Saccharomyces cerevisiae, LCMT2 (TYW4) methoxycarbonylates yW-58 (7-((3S)-3-amino-3-(methoxycarbonyl)propyl)wyosine) at nucleotide 37 of tRNA(Phe) yielding yW (wybutosine). A molecule of carbon dioxide is incorporated during the reaction. | |||
| R-HSA-6782893 (Reactome) | As inferred from homologs in Saccharomyces cerevisiae, TRM12 transfers an aminocarboxypropyl group from S-adenosymethionine to yW-187 (4-demethylwyosine) at nucleotide 37 of tRNA(Phe), yielding yW-86 (7-((3S)-3-amino-3-carboxypropyl)-4-demethylwyosine) and S-methyl-5'-thioadenosine. | |||
| R-HSA-6782895 (Reactome) | As inferred from homologs in Saccharomyces cerevisiae, TYW1 in a complex with FMN and an iron-sulfur cluster transfers 2 carbon atoms from pyruvate to 1-methylguanosine-37 of tRNA(Phe), yielding yW-187 (4-demethylwyosine) at nucleotide 37. | |||
| R-HSA-6783455 (Reactome) | TYW5 uses 2-oxoglutarate and molecular oxygen to hydroxylate yW-72 (7-(3-amino-3-carboxypropyl)wyosine) at nucleotide 37 of tRNA(Phe), yielding OHyW-72 (7-(2-hydroxy-3-amino-3-carboxypropyl)wyosine), carbon dioxide, and succinate (Noma et al. 2010, Kato et al. 2011). | |||
| R-HSA-6783473 (Reactome) | LCMT2 (TYW4) methoxycarbonylates OHyW-72 (7-(2-hydroxy-3-amino-3-carboxypropyl)wyosine) at nucleotide 37 of tRNA(Phe), yielding OHyW (hydroxywybutosine) (Noma et al. 2010). | |||
| SUCCA | Arrow | R-HSA-6783455 (Reactome) | ||
| TRMT12 | mim-catalysis | R-HSA-6782893 (Reactome) | ||
| TRMT5 | mim-catalysis | R-HSA-6782859 (Reactome) | ||
| TYW1:FMN:4Fe-4S | mim-catalysis | R-HSA-6782895 (Reactome) | ||
| TYW3 | mim-catalysis | R-HSA-6782879 (Reactome) | ||
| TYW5:Fe2+ dimer | mim-catalysis | R-HSA-6783455 (Reactome) | ||
| pyruvate | R-HSA-6782895 (Reactome) | |||
| tRNA(Phe) containing 1-methylG-37 | Arrow | R-HSA-6782859 (Reactome) | ||
| tRNA(Phe) containing 1-methylG-37 | R-HSA-6782895 (Reactome) | |||
| tRNA(Phe) containing G-37 | R-HSA-6782859 (Reactome) | |||
| tRNA(Phe) containing OHyW at 37 | Arrow | R-HSA-6783473 (Reactome) | ||
| tRNA(Phe) containing OHyW-72 at 37 | Arrow | R-HSA-6783455 (Reactome) | ||
| tRNA(Phe) containing OHyW-72 at 37 | R-HSA-6783473 (Reactome) | |||
| tRNA(Phe) containing yW at 37 | Arrow | R-HSA-6782890 (Reactome) | ||
| tRNA(Phe) containing yW-187 at 37 | Arrow | R-HSA-6782895 (Reactome) | ||
| tRNA(Phe) containing yW-187 at 37 | R-HSA-6782893 (Reactome) | |||
| tRNA(Phe) containing yW-58 at 37 | Arrow | R-HSA-6782881 (Reactome) | ||
| tRNA(Phe) containing yW-58 at 37 | R-HSA-6782890 (Reactome) | |||
| tRNA(Phe) containing yW-72 at 37 | Arrow | R-HSA-6782879 (Reactome) | ||
| tRNA(Phe) containing yW-72 at 37 | R-HSA-6782881 (Reactome) | |||
| tRNA(Phe) containing yW-72 at 37 | R-HSA-6783455 (Reactome) | |||
| tRNA(Phe) containing yW-86 at 37 | Arrow | R-HSA-6782893 (Reactome) | ||
| tRNA(Phe) containing yW-86 at 37 | R-HSA-6782879 (Reactome) |
