met9 (UniProt Q10258) encodes one of two non-redundant methylenetetrahydrofolate reductases (MTHFR; EC 1.5.1.53) of fission yeast, met9 and met11. Using FAD and NAD(P)H, it reduces 5,10-methylene-THF to 5-methyl-THF, the methyl donor for methionine synthase (met26). The two genes cannot complement each other, and both mutants need methionine. met9 provides the major share (80-85%) of cellular MTHFR activity; met9 disruptants need more methionine for growth and for mating and sporulation than met11 disruptants. Why both enzymes are needed is not clear.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004489 methylenetetrahydrofolate reductase [NAD(P)H] activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference; consistent. Supporting Evidence: PMID:12112238 we defined two genes, met9 and met11, which both encode a methylenetetrahydrofolate reductase |
| GO:0004489 methylenetetrahydrofolate reductase [NAD(P)H] activity | IEA GO_REF:0000120 | ACCEPT | Summary: EC/RHEA and InterPro mapping; consistent. Supporting Evidence: PMID:12112238 we defined two genes, met9 and met11, which both encode a methylenetetrahydrofolate reductase |
| GO:0004489 methylenetetrahydrofolate reductase [NAD(P)H] activity | IMP PMID:12112238 Two non-complementing genes encoding enzymatically active me... | ACCEPT | Summary: Both met9 and met11 encode active MTHFRs; met9 supplies the major share (80-85%) of cellular activity. Supporting Evidence: PMID:12112238 we defined two genes, met9 and met11, which both encode a methylenetetrahydrofolate reductase PMID:12112238 In vitro measurements of enzymatic activities showed that the met11-encoded enzyme was responsible for only 15-20% of the total methylenetetrahydrofolate reductase activity. |
| GO:0005739 mitochondrion | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Similarity transfer of mitochondrial location from S. cerevisiae MET13 (proteomics). MTHFR acts in the cytosolic folate pathway. Reason: Not part of the core function. Supporting Evidence: PMID:12112238 we defined two genes, met9 and met11, which both encode a methylenetetrahydrofolate reductase |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of cytosolic location. Supporting Evidence: PMID:12112238 we defined two genes, met9 and met11, which both encode a methylenetetrahydrofolate reductase |
| GO:0006555 L-methionine metabolic process | IEA GO_REF:0000002 | TOO GENERAL | Summary: Broad parent of methionine biosynthesis. Supporting Evidence: PMID:12112238 we defined two genes, met9 and met11, which both encode a methylenetetrahydrofolate reductase |
| GO:0035999 folate cycle | EXP PMID:12112238 Two non-complementing genes encoding enzymatically active me... | ACCEPT | Summary: MTHFR makes 5-methyl-THF for the methionine synthase step. Supporting Evidence: PMID:12112238 we defined two genes, met9 and met11, which both encode a methylenetetrahydrofolate reductase |
| GO:0035999 folate cycle | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference; consistent. Supporting Evidence: PMID:12112238 we defined two genes, met9 and met11, which both encode a methylenetetrahydrofolate reductase |
| GO:0035999 folate cycle | IEA GO_REF:0000120 | ACCEPT | Summary: ARBA/UniPathway mapping; consistent. Supporting Evidence: PMID:12112238 we defined two genes, met9 and met11, which both encode a methylenetetrahydrofolate reductase |
| GO:0071265 L-methionine biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference; MTHFR supplies methyl groups for methionine synthesis, and its mutants are methionine auxotrophs. Supporting Evidence: PMID:12112238 we defined two genes, met9 and met11, which both encode a methylenetetrahydrofolate reductase |
| GO:0071949 FAD binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: FAD cofactor; subsidiary. Supporting Evidence: PMID:12112238 we defined two genes, met9 and met11, which both encode a methylenetetrahydrofolate reductase |
| GO:0106312 methylenetetrahydrofolate reductase (NADH) activity | IEA GO_REF:0000116 | KEEP AS NON CORE | Summary: RHEA mapping of the NADH reaction; fungal MTHFRs prefer NADPH. Supporting Evidence: PMID:12112238 we defined two genes, met9 and met11, which both encode a methylenetetrahydrofolate reductase |
| GO:0106313 methylenetetrahydrofolate reductase (NADPH) activity | IEA GO_REF:0000116 | ACCEPT | Summary: RHEA/EC mapping of the NADPH-dependent reaction. Supporting Evidence: PMID:12112238 we defined two genes, met9 and met11, which both encode a methylenetetrahydrofolate reductase |
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Download this section (compressed HTML)Q: Why are both met9 and met11 MTHFRs required for methionine prototrophy despite both being active: do they form a heteromer, differ in allosteric SAM inhibition, or channel 5-methyl-THF to different methionine synthase pools?
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