FUM1 encodes the single fumarase (fumarate hydratase, EC 4.2.1.2) of Saccharomyces cerevisiae, a homotetrameric class II fumarase that reversibly hydrates fumarate to (S)-malate. One translation product is targeted to mitochondria and processed by the mitochondrial processing peptidase; about 70% remains in the matrix, where it catalyses the fumarate-to-malate step of the tricarboxylic acid cycle, and the rest folds into an import-incompetent form and returns to the cytosol. fum1 mutants are respiratory deficient and excrete fumarate. Upon DNA double-strand breaks, the cytosolic enzyme is recruited to the nucleus and promotes DNA repair in a manner that depends on its catalytic activity and can be replaced by high concentrations of fumarate.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO (fumarase/aspartase family domains) mapping to root 'catalytic activity'; uninformative. Reason: Replace with the specific activity. Proposed replacements: fumarate hydratase activity Supporting Evidence: file:yeast/FUM1/FUM1-uniprot.txt Reaction=(S)-malate = fumarate + H2O; Xref=Rhea:RHEA:12460, |
| GO:0004333 fumarate hydratase activity | EXP PMID:11585823 Mitochondrial and cytosolic isoforms of yeast fumarase are d... | ACCEPT | Summary: Knox et al. (EXP) measured fumarase activity of the processed cytosolic and mitochondrial Fum1p forms. Reason: Experimental evidence. Supporting Evidence: PMID:11585823 a single translation product of the FUM1 gene encoding fumarase is distributed between the cytosol and mitochondria of Saccharomyces cerevisiae file:yeast/FUM1/FUM1-uniprot.txt Reaction=(S)-malate = fumarate + H2O; Xref=Rhea:RHEA:12460, |
| GO:0004333 fumarate hydratase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA fumarate hydratase activity (PTN000154499, class II fumarases); Fum1p has direct evidence. Reason: Core activity. Supporting Evidence: file:yeast/FUM1/FUM1-uniprot.txt Reaction=(S)-malate = fumarate + H2O; Xref=Rhea:RHEA:12460, PMID:3040736 this gene is concluded to code for yeast fumarase |
| GO:0004333 fumarate hydratase activity | IDA PMID:20231875 Fumarase: a mitochondrial metabolic enzyme and a cytosolic/n... | ACCEPT | Summary: Yogev et al. assayed fumarase activity and used catalytically inactive mutants to show DNA-damage protection requires activity. Reason: Direct evidence. Supporting Evidence: PMID:20231875 This function of fumarase depends on its enzymatic activity, and its absence in cells can be complemented by high concentrations of fumaric acid. |
| GO:0004333 fumarate hydratase activity | IDA PMID:3040736 Mitochondrial and cytoplasmic fumarases in Saccharomyces cer... | ACCEPT | Summary: Wu & Tzagoloff: FUM1 complements fumarase-deficient pet mutants and overexpression elevates fumarase activity; mutations abolish both mitochondrial and cytosolic activities. Reason: Direct evidence. Supporting Evidence: PMID:3040736 Mutations in FUM1 simultaneously abolish both activities. PMID:3040736 this gene is concluded to code for yeast fumarase |
| GO:0004333 fumarate hydratase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (InterPro IPR005677, Rhea:12460, EC 4.2.1.2); correct. Reason: Core activity. Supporting Evidence: file:yeast/FUM1/FUM1-uniprot.txt Reaction=(S)-malate = fumarate + H2O; Xref=Rhea:RHEA:12460, |
| GO:0004333 fumarate hydratase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA from the TCA/glyoxylate superpathway; correct activity. Reason: Correct activity class. Supporting Evidence: file:yeast/FUM1/FUM1-uniprot.txt Reaction=(S)-malate = fumarate + H2O; Xref=Rhea:RHEA:12460, |
| GO:0004333 fumarate hydratase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA from TCA-EUK-PWY; correct activity in the correct pathway. Reason: Correct. Supporting Evidence: file:yeast/FUM1/FUM1-uniprot.txt Reaction=(S)-malate = fumarate + H2O; Xref=Rhea:RHEA:12460, |
| GO:0005515 protein binding | IPI PMID:11805837 Systematic identification of protein complexes in Saccharomy... | REMOVE | Summary: Large-scale TAP-MS complex survey (Ho et al. 2002) reporting a co-purification. 'protein binding' carries no functional information about Fum1p. Reason: Uninformative term per curation policy; removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: Large-scale binary interactome (Michaelis et al. 2023) reporting a Fum1p interaction; 'protein binding' is uninformative. Reason: Uninformative term per curation policy; removal does not imply the interaction is false. |
| GO:0005634 nucleus | IDA PMID:20231875 Fumarase: a mitochondrial metabolic enzyme and a cytosolic/n... | ACCEPT | Summary: Yogev et al.: cytosolic fumarase is recruited to the nucleus upon DNA damage, where it functions in the DSB response. Reason: Experimental, condition-dependent location of the cytosolic pool. Supporting Evidence: PMID:20231875 We show that the cytosolic fumarase is a member of the DNA damage response that is recruited from the cytosol to the nucleus upon DNA damage induction. |
| GO:0005634 nucleus | IDA PMID:20231875 Fumarase: a mitochondrial metabolic enzyme and a cytosolic/n... | ACCEPT | Summary: Same evidence (located_in nucleus) from Yogev et al. Reason: Experimental; DNA damage-induced nuclear pool. Supporting Evidence: PMID:20231875 We show that the cytosolic fumarase is a member of the DNA damage response that is recruited from the cytosol to the nucleus upon DNA damage induction. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping to nucleus; reflects the DNA damage-induced nuclear pool. Reason: Supported by experimental nuclear recruitment. Supporting Evidence: PMID:20231875 We show that the cytosolic fumarase is a member of the DNA damage response that is recruited from the cytosol to the nucleus upon DNA damage induction. |
| GO:0005737 cytoplasm | EXP PMID:11585823 Mitochondrial and cytosolic isoforms of yeast fumarase are d... | ACCEPT | Summary: Knox et al. (EXP): processed Fum1p is distributed between mitochondria and cytosol. Reason: Experimental location. Supporting Evidence: PMID:11585823 a single translation product of the FUM1 gene encoding fumarase is distributed between the cytosol and mitochondria of Saccharomyces cerevisiae |
| GO:0005737 cytoplasm | EXP PMID:20231875 Fumarase: a mitochondrial metabolic enzyme and a cytosolic/n... | ACCEPT | Summary: Yogev et al. (EXP): cytosolic fumarase pool documented. Reason: Experimental location. Supporting Evidence: PMID:20231875 We show that the cytosolic fumarase is a member of the DNA damage response that is recruited from the cytosol to the nucleus upon DNA damage induction. |
| GO:0005737 cytoplasm | EXP PMID:3040736 Mitochondrial and cytoplasmic fumarases in Saccharomyces cer... | ACCEPT | Summary: Wu & Tzagoloff (EXP): fumarase detected in the soluble postribosomal fraction as well as mitochondria. Reason: Experimental location. Supporting Evidence: PMID:3040736 In wild type yeast, fumarase is detected in both mitochondria and the soluble postribosomal protein fraction. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping to cytoplasm; correct. Reason: Correct. Supporting Evidence: PMID:11585823 a single translation product of the FUM1 gene encoding fumarase is distributed between the cytosol and mitochondria of Saccharomyces cerevisiae |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | ACCEPT | Summary: Mitochondrial proteome (Reinders et al. 2006) detected Fum1p. Reason: Correct. Supporting Evidence: file:yeast/FUM1/FUM1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005739 mitochondrion | HDA PMID:24769239 Quantitative variations of the mitochondrial proteome and ph... | ACCEPT | Summary: Quantitative mitochondrial proteome (Renvoise et al. 2014) detected Fum1p. Reason: Correct. Supporting Evidence: file:yeast/FUM1/FUM1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA is_active_in mitochondrion; correct. Reason: Correct. Supporting Evidence: file:yeast/FUM1/FUM1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005739 mitochondrion | IDA PMID:11502169 Yeast mitochondrial dehydrogenases are associated in a supra... | ACCEPT | Summary: Grandier-Vazeille et al. found Fum1p in a mitochondrial supramolecular complex with other TCA enzymes and dehydrogenases. Reason: Direct observation. Supporting Evidence: PMID:11502169 four tricarboxylic acids cycle enzymes (malate dehydrogenase Mdh1p, citrate synthase Cit1p, succinate dehydrogenase Sdh1p, and fumarate hydratase Fum1p) |
| GO:0005739 mitochondrion | IDA PMID:20231875 Fumarase: a mitochondrial metabolic enzyme and a cytosolic/n... | ACCEPT | Summary: Yogev et al. confirmed mitochondrial Fum1p (strains with exclusively mitochondrial fumarase were constructed). Reason: Experimental. Supporting Evidence: PMID:20231875 the yeast cytosolic fumarase plays a key role in the protection of cells from DNA damage, particularly from DNA double-strand breaks |
| GO:0005739 mitochondrion | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA is_active_in mitochondrion from TCA-EUK-PWY; correct. Reason: Correct. Supporting Evidence: file:yeast/FUM1/FUM1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005759 mitochondrial matrix | EXP PMID:20231875 Fumarase: a mitochondrial metabolic enzyme and a cytosolic/n... | ACCEPT | Summary: Yogev et al. (EXP) mitochondrial matrix localisation. Reason: Correct. Supporting Evidence: file:yeast/FUM1/FUM1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005759 mitochondrial matrix | EXP PMID:3040736 Mitochondrial and cytoplasmic fumarases in Saccharomyces cer... | ACCEPT | Summary: Wu & Tzagoloff (EXP) matrix fumarase. Reason: Correct. Supporting Evidence: PMID:3040736 In wild type yeast, fumarase is detected in both mitochondria and the soluble postribosomal protein fraction. |
| GO:0005759 mitochondrial matrix | IDA PMID:11585823 Mitochondrial and cytosolic isoforms of yeast fumarase are d... | ACCEPT | Summary: Knox et al.: mitochondrial Fum1p is processed by the matrix processing peptidase. Reason: Correct. Supporting Evidence: PMID:11585823 fumarase cytosolic and mitochondrial isoenzymes have an identical amino terminus that is formed by cleavage by the mitochondrial processing peptidase |
| GO:0005759 mitochondrial matrix | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping to mitochondrial matrix; correct. Reason: Correct. Supporting Evidence: file:yeast/FUM1/FUM1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005829 cytosol | IDA PMID:11585823 Mitochondrial and cytosolic isoforms of yeast fumarase are d... | ACCEPT | Summary: Knox et al.: a large fraction of processed fumarase is cytosolic. Reason: Experimental location. Supporting Evidence: PMID:11585823 a single translation product of the FUM1 gene encoding fumarase is distributed between the cytosol and mitochondria of Saccharomyces cerevisiae |
| GO:0005829 cytosol | IDA PMID:20231875 Fumarase: a mitochondrial metabolic enzyme and a cytosolic/n... | ACCEPT | Summary: Yogev et al.: cytosolic fumarase pool documented. Reason: Experimental location. Supporting Evidence: PMID:20231875 the yeast cytosolic fumarase plays a key role in the protection of cells from DNA damage, particularly from DNA double-strand breaks |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA is_active_in cytosol from the superpathway; the cytosolic fumarase pool is real, though its metabolic pathway role there is not the TCA cycle. Reason: Location supported. Supporting Evidence: PMID:11585823 a single translation product of the FUM1 gene encoding fumarase is distributed between the cytosol and mitochondria of Saccharomyces cerevisiae |
| GO:0006099 tricarboxylic acid cycle | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA tricarboxylic acid cycle; Fum1p is the only fumarase and the TCA-cycle enzyme. Reason: Core process. Supporting Evidence: file:yeast/FUM1/FUM1-uniprot.txt Reaction=(S)-malate = fumarate + H2O; Xref=Rhea:RHEA:12460, |
| GO:0006099 tricarboxylic acid cycle | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (ARBA, InterPro, UniPathway) TCA cycle; correct. Reason: Core process. Supporting Evidence: file:yeast/FUM1/FUM1-uniprot.txt Reaction=(S)-malate = fumarate + H2O; Xref=Rhea:RHEA:12460, |
| GO:0006099 tricarboxylic acid cycle | IMP PMID:1587456 Fumaric acid overproduction in yeast mutants deficient in fu... | ACCEPT | Summary: Kaclikova et al.: a fumarase-deficient mutant accumulates fumaric acid in a manner requiring succinate dehydrogenase-to-oxygen electron transport, i.e. TCA flux is blocked at fumarase. Reason: Mutant phenotype supports TCA role. Supporting Evidence: PMID:1587456 Cells of the fumarase-deficient mutant fermenting glucose accumulated extracellular fumaric acid. |
| GO:0006106 fumarate metabolic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT IBA fumarate metabolic process; correct (Fum1p interconverts fumarate) but more general than TCA cycle. Reason: Correct but general. Supporting Evidence: file:yeast/FUM1/FUM1-uniprot.txt Reaction=(S)-malate = fumarate + H2O; Xref=Rhea:RHEA:12460, |
| GO:0006106 fumarate metabolic process | IDA PMID:20231875 Fumarase: a mitochondrial metabolic enzyme and a cytosolic/n... | KEEP AS NON CORE | Summary: Yogev et al.: nuclear DNA-damage function depends on fumarase converting malate/fumarate; IDA for fumarate metabolism. Reason: Correct but general. Supporting Evidence: PMID:20231875 This function of fumarase depends on its enzymatic activity, and its absence in cells can be complemented by high concentrations of fumaric acid. |
| GO:0006106 fumarate metabolic process | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro2GO (IPR005677 fumarate hydratase class II) fumarate metabolic process; correct but general. Reason: Correct but general. Supporting Evidence: file:yeast/FUM1/FUM1-uniprot.txt Reaction=(S)-malate = fumarate + H2O; Xref=Rhea:RHEA:12460, |
| GO:0006106 fumarate metabolic process | IMP PMID:1587456 Fumaric acid overproduction in yeast mutants deficient in fu... | KEEP AS NON CORE | Summary: Kaclikova et al.: fumarase-deficient mutants accumulate fumarate. Reason: Correct but general. Supporting Evidence: PMID:1587456 Cells of the fumarase-deficient mutant fermenting glucose accumulated extracellular fumaric acid. |
| GO:0006108 malate metabolic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT IBA malate metabolic process; correct (product is (S)-malate) but general. Reason: Correct but general. Supporting Evidence: file:yeast/FUM1/FUM1-uniprot.txt Reaction=(S)-malate = fumarate + H2O; Xref=Rhea:RHEA:12460, |
| GO:0006302 double-strand break repair | IDA PMID:20231875 Fumarase: a mitochondrial metabolic enzyme and a cytosolic/n... | ACCEPT | Summary: Yogev et al.: cytosolic fumarase protects cells from DNA double-strand breaks and is recruited to the nucleus; function requires catalytic activity and is rescued by fumarate. Moonlighting role of the cytosolic pool. Reason: Experimental; second, compartment-specific role of the cytosolic/nuclear pool. Supporting Evidence: PMID:20231875 the yeast cytosolic fumarase plays a key role in the protection of cells from DNA damage, particularly from DNA double-strand breaks PMID:20231875 This function of fumarase depends on its enzymatic activity, and its absence in cells can be complemented by high concentrations of fumaric acid. |
| GO:0006974 DNA damage response | IDA PMID:20231875 Fumarase: a mitochondrial metabolic enzyme and a cytosolic/n... | KEEP AS NON CORE | Summary: Yogev et al.: fumarase is a member of the DNA damage response. Reason: Experimental; secondary role. Supporting Evidence: PMID:20231875 We show that the cytosolic fumarase is a member of the DNA damage response that is recruited from the cytosol to the nucleus upon DNA damage induction. |
| GO:0009060 aerobic respiration | RCA GO_REF:0000123 | KEEP AS NON CORE | Summary: YeastPathways RCA aerobic respiration from TCA-EUK-PWY; correct parent of TCA cycle but less specific. Reason: Correct but general. Supporting Evidence: PMID:1587456 Cells of the fumarase-deficient mutant fermenting glucose accumulated extracellular fumaric acid. |
| GO:0016829 lyase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO (IPR018951 fumarase C-terminal) mapping to 'lyase activity'; correct but uninformative. Reason: Replace with the specific activity. Proposed replacements: fumarate hydratase activity Supporting Evidence: file:yeast/FUM1/FUM1-uniprot.txt Reaction=(S)-malate = fumarate + H2O; Xref=Rhea:RHEA:12460, |
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