Cobalamin-independent methionine synthase (MetE; 5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase, EC 2.1.1.14) of Saccharomyces cerevisiae. Met6 transfers the methyl group of 5-methyltetrahydropteroyl tri-L-glutamate to L-homocysteine, forming L-methionine; this is the final step of de novo methionine synthesis and the remethylation step of the S-adenosylmethionine (methyl) cycle. Yeast has no cobalamin-dependent MetH, so Met6 is the only methionine synthase and met6 mutants are methionine auxotrophs. Met6 is a zinc-dependent, very abundant cytoplasmic enzyme.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000097 sulfur amino acid biosynthetic process | RCA GO_REF:0000123 | TOO GENERAL | Summary: YeastPathways RCA (PWY-821-1); Met6 catalyses the final step of methionine synthesis. Correct but broad. Reason: Broad parent. Supporting Evidence: file:yeast/MET6/MET6-uniprot.txt pathway; L-methionine from L-homocysteine (MetE route): step 1/1. |
| GO:0003871 5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for cobalamin-independent methionine synthase (MetE) activity; Met6 is the sole yeast MetE. Supporting Evidence: file:yeast/MET6/MET6-uniprot.txt Reaction=5-methyltetrahydropteroyltri-L-glutamate + L-homocysteine = file:yeast/MET6/MET6-uniprot.txt SIMILARITY: Belongs to the vitamin-B12 independent methionine synthase file:yeast/MET6/MET6-uniprot.txt pathway; L-methionine from L-homocysteine (MetE route): step 1/1. |
| GO:0003871 5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: EC 2.1.1.14/RHEA:21196 mapping; correct. Supporting Evidence: file:yeast/MET6/MET6-uniprot.txt Reaction=5-methyltetrahydropteroyltri-L-glutamate + L-homocysteine = file:yeast/MET6/MET6-uniprot.txt SIMILARITY: Belongs to the vitamin-B12 independent methionine synthase file:yeast/MET6/MET6-uniprot.txt pathway; L-methionine from L-homocysteine (MetE route): step 1/1. |
| GO:0003871 5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase activity | IMP PMID:3542720 Molecular cloning and characterization of the MET6 gene of S... | ACCEPT | Summary: MET6 was cloned by complementing a met6 methionine auxotroph (abstract-only; curator-read). The abstract's suggestion of a regulatory role is not borne out, but the methionine synthase assignment is standard. Supporting Evidence: PMID:3542720 A yeast DNA fragment complementing the met6 mutation in yeast (Saccharomyces cerevisiae) was cloned in a shuttle vector file:yeast/MET6/MET6-uniprot.txt Reaction=5-methyltetrahydropteroyltri-L-glutamate + L-homocysteine = |
| GO:0003871 5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (P4-PWY-1 (superpathway of lysine, threonine and methionine biosynthesis)) asserting MetE activity for Met6; correct. Supporting Evidence: file:yeast/MET6/MET6-uniprot.txt Reaction=5-methyltetrahydropteroyltri-L-glutamate + L-homocysteine = file:yeast/MET6/MET6-uniprot.txt SIMILARITY: Belongs to the vitamin-B12 independent methionine synthase file:yeast/MET6/MET6-uniprot.txt pathway; L-methionine from L-homocysteine (MetE route): step 1/1. |
| GO:0003871 5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (PWY-5041 (S-adenosyl-L-methionine cycle II)) asserting MetE activity for Met6; correct. Supporting Evidence: file:yeast/MET6/MET6-uniprot.txt Reaction=5-methyltetrahydropteroyltri-L-glutamate + L-homocysteine = file:yeast/MET6/MET6-uniprot.txt SIMILARITY: Belongs to the vitamin-B12 independent methionine synthase file:yeast/MET6/MET6-uniprot.txt pathway; L-methionine from L-homocysteine (MetE route): step 1/1. |
| GO:0003871 5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (PWY-821-1 (superpathway of sulfur amino acid biosynthesis)) asserting MetE activity for Met6; correct. Supporting Evidence: file:yeast/MET6/MET6-uniprot.txt Reaction=5-methyltetrahydropteroyltri-L-glutamate + L-homocysteine = file:yeast/MET6/MET6-uniprot.txt SIMILARITY: Belongs to the vitamin-B12 independent methionine synthase file:yeast/MET6/MET6-uniprot.txt pathway; L-methionine from L-homocysteine (MetE route): step 1/1. |
| GO:0003871 5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (PWY3O-238 (methionine biosynthesis)) asserting MetE activity for Met6; correct. Supporting Evidence: file:yeast/MET6/MET6-uniprot.txt Reaction=5-methyltetrahydropteroyltri-L-glutamate + L-homocysteine = file:yeast/MET6/MET6-uniprot.txt SIMILARITY: Belongs to the vitamin-B12 independent methionine synthase file:yeast/MET6/MET6-uniprot.txt pathway; L-methionine from L-homocysteine (MetE route): step 1/1. |
| GO:0003871 5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (PWY3O-954 (superpathway of methionine biosynthesis)) asserting MetE activity for Met6; correct. Supporting Evidence: file:yeast/MET6/MET6-uniprot.txt Reaction=5-methyltetrahydropteroyltri-L-glutamate + L-homocysteine = file:yeast/MET6/MET6-uniprot.txt SIMILARITY: Belongs to the vitamin-B12 independent methionine synthase file:yeast/MET6/MET6-uniprot.txt pathway; L-methionine from L-homocysteine (MetE route): step 1/1. |
| GO:0005737 cytoplasm | HDA PMID:14562095 Global analysis of protein localization in budding yeast. | ACCEPT | Summary: Huh et al. GFP localisation in the cytoplasm. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA (is_active_in cytosol) for MetE; consistent with experimental cytoplasmic localisation. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (P4-PWY-1 (superpathway of lysine, threonine and methionine biosynthesis)) cytosolic placement; consistent with GFP data. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (PWY-5041 (S-adenosyl-L-methionine cycle II)) cytosolic placement; consistent with GFP data. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (PWY-821-1 (superpathway of sulfur amino acid biosynthesis)) cytosolic placement; consistent with GFP data. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (PWY3O-238 (methionine biosynthesis)) cytosolic placement; consistent with GFP data. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (PWY3O-954 (superpathway of methionine biosynthesis)) cytosolic placement; consistent with GFP data. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories |
| GO:0005886 plasma membrane | HDA PMID:16622836 The plasma membrane proteome of Saccharomyces cerevisiae and... | MARK AS OVER ANNOTATED | Summary: Plasma-membrane fraction proteomics (Delom et al.). Met6 is one of the most abundant soluble proteins in yeast (~264,000 copies/cell), so detection in a membrane fraction is most likely contamination. Reason: Likely contaminant of a high-throughput membrane proteome. Supporting Evidence: PMID:16622836 Proteins from a stripped plasma membrane fraction were solubilized with the neutral and non-denaturing detergent file:yeast/MET6/MET6-uniprot.txt Present with 264000 molecules/cell in log phase SD |
| GO:0006566 L-threonine metabolic process | RCA GO_REF:0000123 | REMOVE | Summary: YeastPathways RCA inherited from P4-PWY-1. Met6 methylates homocysteine to methionine; it plays no part in threonine metabolism. Reason: Superpathway inheritance. Supporting Evidence: file:yeast/MET6/MET6-uniprot.txt Reaction=5-methyltetrahydropteroyltri-L-glutamate + L-homocysteine = |
| GO:0008270 zinc ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro (MetE domains) zinc ion binding; MetE requires a catalytic zinc. Reason: Catalytic cofactor binding; non-core. Supporting Evidence: file:yeast/MET6/MET6-uniprot.txt Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250}; |
| GO:0008270 zinc ion binding | RCA PMID:30358795 The cellular economy of the Saccharomyces cerevisiae zinc pr... | KEEP AS NON CORE | Summary: Zinc-proteome analysis (Wang et al.) predicted Met6 as a zinc protein and studied its metalation under zinc deficiency. MetE enzymes use a catalytic Zn2+ to activate homocysteine. Reason: Catalytic cofactor binding; non-core. Supporting Evidence: PMID:30358795 Our analysis of two abundant zinc proteins, Fba1 aldolase and Met6 methionine synthetase, supported that hypothesis. file:yeast/MET6/MET6-uniprot.txt Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250}; |
| GO:0008652 amino acid biosynthetic process | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro (IPR013215, MetE N-terminal) amino acid biosynthetic process; correct but general. Reason: Generic parent. Supporting Evidence: file:yeast/MET6/MET6-uniprot.txt pathway; L-methionine from L-homocysteine (MetE route): step 1/1. |
| GO:0008705 methionine synthase activity | IBA GO_REF:0000033 | MODIFY | Summary: PAINT IBA assigning 'methionine synthase activity' (GO:0008705, defined on the monoglutamate 5-methyltetrahydrofolate reaction, EC 2.1.1.13, i.e. the cobalamin-dependent MetH reaction). Met6 is a cobalamin-independent MetE (EC 2.1.1.14), which uses the triglutamate form of 5-methyltetrahydrofolate; S. cerevisiae has no MetH. The precise term is GO:0003871. Reason: MetE family should carry the EC 2.1.1.14 term, not the EC 2.1.1.13 term. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Proposed replacements: 5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase activity Supporting Evidence: file:yeast/MET6/MET6-uniprot.txt Reaction=5-methyltetrahydropteroyltri-L-glutamate + L-homocysteine = file:yeast/MET6/MET6-uniprot.txt SIMILARITY: Belongs to the vitamin-B12 independent methionine synthase file:yeast/MET6/MET6-uniprot.txt pathway; L-methionine from L-homocysteine (MetE route): step 1/1. |
| GO:0033353 L-methionine cycle | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (PWY-5041 S-adenosyl-L-methionine cycle II). Met6 remethylates homocysteine produced from S-adenosylhomocysteine, closing the methyl cycle; this is a direct catalytic step. Supporting Evidence: file:yeast/MET6/MET6-uniprot.txt Reaction=5-methyltetrahydropteroyltri-L-glutamate + L-homocysteine = |
| GO:0071265 L-methionine biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for methionine biosynthesis; correct. Supporting Evidence: file:yeast/MET6/MET6-uniprot.txt Reaction=5-methyltetrahydropteroyltri-L-glutamate + L-homocysteine = file:yeast/MET6/MET6-uniprot.txt SIMILARITY: Belongs to the vitamin-B12 independent methionine synthase file:yeast/MET6/MET6-uniprot.txt pathway; L-methionine from L-homocysteine (MetE route): step 1/1. |
| GO:0071265 L-methionine biosynthetic process | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA mapping to methionine biosynthesis; correct. Supporting Evidence: file:yeast/MET6/MET6-uniprot.txt Reaction=5-methyltetrahydropteroyltri-L-glutamate + L-homocysteine = file:yeast/MET6/MET6-uniprot.txt SIMILARITY: Belongs to the vitamin-B12 independent methionine synthase file:yeast/MET6/MET6-uniprot.txt pathway; L-methionine from L-homocysteine (MetE route): step 1/1. |
| GO:0071265 L-methionine biosynthetic process | IMP PMID:1101032 Methionine biosynthesis in Saccharomyces cerevisiae. I. Gene... | ACCEPT | Summary: Complementation analysis of methionine auxotrophs including met6. Supporting Evidence: PMID:1101032 In order to analyse how many structural genes are implicated in the specific steps of the biosynthesis of methionine in Sacch. cerevisiae, a hundred mutants were studied by complementation. PMID:3542720 A yeast DNA fragment complementing the met6 mutation in yeast (Saccharomyces cerevisiae) was cloned in a shuttle vector |
| GO:0071265 L-methionine biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (PWY3O-238 (methionine biosynthesis)) for methionine biosynthesis; Met6 catalyses the final step. Supporting Evidence: file:yeast/MET6/MET6-uniprot.txt Reaction=5-methyltetrahydropteroyltri-L-glutamate + L-homocysteine = file:yeast/MET6/MET6-uniprot.txt SIMILARITY: Belongs to the vitamin-B12 independent methionine synthase file:yeast/MET6/MET6-uniprot.txt pathway; L-methionine from L-homocysteine (MetE route): step 1/1. |
| GO:0071265 L-methionine biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (PWY3O-954 (superpathway of methionine biosynthesis)) for methionine biosynthesis; Met6 catalyses the final step. Supporting Evidence: file:yeast/MET6/MET6-uniprot.txt Reaction=5-methyltetrahydropteroyltri-L-glutamate + L-homocysteine = file:yeast/MET6/MET6-uniprot.txt SIMILARITY: Belongs to the vitamin-B12 independent methionine synthase file:yeast/MET6/MET6-uniprot.txt pathway; L-methionine from L-homocysteine (MetE route): step 1/1. |
| GO:0071267 L-methionine salvage | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: IEA inferred from GO:0008705 part_of L-methionine salvage. Met6 does regenerate methionine from homocysteine recycled through the SAM cycle, which fits the broad salvage definition, but the inference rests on the mis-assigned MetH term and 'salvage' usually denotes the MTA cycle (5'-methylthioadenosine to methionine), which Met6 does not catalyse. Reason: Indirect inference; methionine cycle (GO:0033353) is the better description. Supporting Evidence: file:yeast/MET6/MET6-uniprot.txt Reaction=5-methyltetrahydropteroyltri-L-glutamate + L-homocysteine = |
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Cobalamin-independent methionine synthase; involved in methionine biosynthesis and regeneration; requires a minimum of two glutamates on the methyltetrahydrofolate substrate, similar to bacterial metE homologs
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