S-methyl-5'-thioadenosine phosphorylase (MTAP, EC 2.4.2.28) of Saccharomyces cerevisiae, a homotrimeric PNP/MTAP-family enzyme that phosphorolyses 5'-methylthioadenosine (MTA), the by-product of spermidine/spermine synthesis, to adenine and 5-methylthioribose 1-phosphate. This is the entry step of the methionine salvage pathway and also recycles adenine. meu1 deletion abolishes MTAP activity, causes MTA accumulation, and raises ornithine decarboxylase activity and polyamine pools, because downstream salvage metabolites (notably 4-methylthio-2-oxobutanoate) feed back to repress ODC. MEU1 was first isolated as a multicopy enhancer of UAS2-dependent ADH2 expression. Meu1 is a cytoplasmic/nuclear soluble protein that has also been recovered bound to its own mRNA.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003729 mRNA binding | IDA PMID:21124907 A screen for RNA-binding proteins in yeast indicates dual fu... | KEEP AS NON CORE | Summary: Tsvetanova 2010 protein-microarray RBP screen with follow-up RIP: Meu1 was among enzymes found associated with their own mRNA. Biological significance is unknown. Reason: Experimentally observed but of unknown functional relevance; not part of MTAP function. Supporting Evidence: PMID:21124907 Four of the 13 proteins (30%) were associated with their own mRNA (Pfk2, Pre2, Map1, Meu1). |
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro PNP/MTAP domain mapping to root catalytic activity; true but uninformative. Reason: Replace with the specific phosphorylase activity. Proposed replacements: S-methyl-5-thioadenosine phosphorylase activity |
| GO:0005634 nucleus | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: UniRule/SubCell IEA nucleus (UniProt: Cytoplasm. Nucleus.). Small soluble enzyme; no nuclear role known. Reason: Localization, non-core. |
| GO:0005737 cytoplasm | IDA PMID:8807288 Isolation and identification of genes activating UAS2-depend... | ACCEPT | Summary: Donoviel & Young 1996: a Meu1/beta-gal fusion showed diffuse, non-compartmentalised (cytoplasmic) distribution. Supporting Evidence: PMID:8807288 A MEU1/beta-gal fusion protein was not localized to a particular region of the cell. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: UniRule/SubCell IEA cytoplasm; consistent. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA cytosol (is_active_in) from human MTAP (Q13126); MTAP is a cytosolic enzyme. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (PWY3O-351) placing MTAP in cytosol. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (PWY3O-64) placing MTAP in cytosol. |
| GO:0009116 nucleoside metabolic process | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro mapping to nucleoside metabolic process; MTA is a nucleoside and MTAP also releases adenine for purine salvage. Correct but generic. Reason: Generic parent-type process; the core process is methionine salvage. |
| GO:0016763 pentosyltransferase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro IPR018099 (purine phosphorylase family 2 conserved site) mapping to pentosyltransferase activity; true parent of the MTAP activity. Reason: Use the specific activity. Proposed replacements: S-methyl-5-thioadenosine phosphorylase activity |
| GO:0017061 S-methyl-5-thioadenosine phosphorylase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for MTAP activity (donors include Meu1 itself, human MTAP, mouse/rat/fly orthologues); core. Supporting Evidence: file:yeast/MEU1/MEU1-uniprot.txt Reaction=S-methyl-5'-thioadenosine + phosphate = 5-(methylsulfanyl)- file:yeast/MEU1/MEU1-uniprot.txt SIMILARITY: Belongs to the PNP/MTAP phosphorylase family. MTAP |
| GO:0017061 S-methyl-5-thioadenosine phosphorylase activity | IDA PMID:14506228 Methylthioadenosine phosphorylase regulates ornithine decarb... | ACCEPT | Summary: SGD IDA (Subhi 2003): MTAP activity attributed to the MEU1 gene product. Supporting Evidence: PMID:14506228 We show that in Saccharomyces cerevisiae the MEU1 gene encodes MTAP and that Meu1delta cells have an 8-fold increase in ODC activity, resulting in large elevations in polyamine pools. |
| GO:0017061 S-methyl-5-thioadenosine phosphorylase activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA via RHEA:11852/EC 2.4.2.28/UniRule; correct. Supporting Evidence: file:yeast/MEU1/MEU1-uniprot.txt Reaction=S-methyl-5'-thioadenosine + phosphate = 5-(methylsulfanyl)- |
| GO:0017061 S-methyl-5-thioadenosine phosphorylase activity | IMP PMID:14506228 Methylthioadenosine phosphorylase regulates ornithine decarb... | ACCEPT | Summary: SGD IMP (Subhi 2003): meu1 deletion abolishes MTAP activity. Supporting Evidence: PMID:14506228 We show that in Saccharomyces cerevisiae the MEU1 gene encodes MTAP and that Meu1delta cells have an 8-fold increase in ODC activity, resulting in large elevations in polyamine pools. |
| GO:0017061 S-methyl-5-thioadenosine phosphorylase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (PWY3O-351) for the MTA phosphorylase step; correct. |
| GO:0017061 S-methyl-5-thioadenosine phosphorylase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (PWY3O-64) for the MTA phosphorylase step; correct. |
| GO:0033353 L-methionine cycle | IBA GO_REF:0000033 | MODIFY | Summary: PAINT IBA for L-methionine cycle; MTAP is the entry enzyme of methionine regeneration from MTA (GO places salvage enzymes under this term). Reason: GO:0033353 denotes the SAM/SAH/homocysteine cycle; Meu1 acts in the MTA-specific methionine salvage branch. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: SGD:S000004007 · yeast MEU1 SUPPORTS TRANSFER Proposed replacements: L-methionine salvage |
| GO:0033353 L-methionine cycle | IDA PMID:14506228 Methylthioadenosine phosphorylase regulates ornithine decarb... | MODIFY | Summary: SGD IDA (Subhi 2003) for L-methionine cycle, based on MTAP activity of Meu1. Reason: MTAP activity supports the MTA-salvage branch, GO:0071267, rather than the SAM/SAH/homocysteine cycle named by GO:0033353. Proposed replacements: L-methionine salvage Supporting Evidence: PMID:14506228 We show that in Saccharomyces cerevisiae the MEU1 gene encodes MTAP and that Meu1delta cells have an 8-fold increase in ODC activity, resulting in large elevations in polyamine pools. |
| GO:0033353 L-methionine cycle | IEA GO_REF:0000104 | MODIFY | Summary: UniRule IEA for L-methionine cycle; consistent. Reason: GO:0033353 denotes the SAM/SAH/homocysteine cycle; GO:0019509 is obsolete in QuickGO, so GO:0071267 is the nearest live MTA-salvage term available. Proposed replacements: L-methionine salvage Supporting Evidence: GO:0019509 QuickGO reports isObsolete=true for obsolete L-methionine salvage from methylthioadenosine. |
| GO:0033353 L-methionine cycle | IMP PMID:14506228 Methylthioadenosine phosphorylase regulates ornithine decarb... | MODIFY | Summary: SGD IMP (Subhi 2003): meu1 and downstream salvage mutants share elevated ODC/polyamine phenotypes. Reason: The phenotype is an MTA-salvage defect; GO:0019509 is obsolete in QuickGO, so GO:0071267 is the nearest live branch term. Proposed replacements: L-methionine salvage Supporting Evidence: PMID:14506228 We show that in Saccharomyces cerevisiae the MEU1 gene encodes MTAP and that Meu1delta cells have an 8-fold increase in ODC activity, resulting in large elevations in polyamine pools. GO:0019509 QuickGO reports isObsolete=true for obsolete L-methionine salvage from methylthioadenosine. PMID:14506228 Mutations in putative salvage pathway genes downstream of MTAP also cause elevated ODC activity and elevated polyamines. |
| GO:0033353 L-methionine cycle | IMP PMID:18625006 A complete inventory of all enzymes in the eukaryotic methio... | MODIFY | Summary: SGD IMP (Pirkov 2008): MEU1 verified as the MTAP step of the salvage cycle by auxotrophy and MTA measurements in deletion mutants. Reason: Pirkov et al. verified Meu1 in the MTA-specific branch, whose MTA-specific GO:0019509 term is obsolete in QuickGO; GO:0071267 is the nearest live branch term. Proposed replacements: L-methionine salvage Supporting Evidence: PMID:18625006 The 5'-methylthioadenosine phosphorylase was verified as Meu1p, the 2,3-dioxomethiopentane-1-phosphate enolase/phosphatase as Utr4p and the aci-reductone dioxygenase as Adi1p. GO:0019509 QuickGO reports isObsolete=true for obsolete L-methionine salvage from methylthioadenosine. PMID:18625006 The methodology used involved auxotrophic growth tests and analysis of intracellular 5'-methylthioadenosine in deletion mutants. |
| GO:0071267 L-methionine salvage | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (PWY3O-351) for L-methionine salvage; Meu1 catalyses the entry step. Supporting Evidence: PMID:18625006 The 5'-methylthioadenosine phosphorylase was verified as Meu1p, the 2,3-dioxomethiopentane-1-phosphate enolase/phosphatase as Utr4p and the aci-reductone dioxygenase as Adi1p. |
| GO:0071267 L-methionine salvage | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (PWY3O-64) for L-methionine salvage; correct. |
| GO:0097054 L-glutamate biosynthetic process | IMP PMID:8807288 Isolation and identification of genes activating UAS2-depend... | UNDECIDED | Summary: SGD IMP from Donoviel & Young 1996 (MEU1 as multicopy enhancer of UAS2-dependent ADH2 expression). The cached abstract reports only ADH2-expression and no-growth-defect phenotypes and does not mention glutamate; the basis of the glutamate-biosynthesis annotation must be in the full text, which we could not read. A direct role of an MTA phosphorylase in glutamate synthesis is not expected biologically, but an experimental curator call cannot be dismissed without the full text. Reason: Full text not available; abstract does not describe a glutamate phenotype. Supporting Evidence: PMID:8807288 Disruption of MEU1 reduced endogenous ADH2 expression about twofold but had no effect on cell viability or growth. |
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Q: Is the reported Meu1 association with its own mRNA functionally relevant (e.g. autoregulation)?
Methylthioadenosine phosphorylase (MTAP); catalyzes the initial step in the methionine salvage pathway; affects polyamine biosynthesis through regulation of ornithine decarboxylase (Spe1p) activity; regulates ADH2 gene expression
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