ICL1 encodes isocitrate lyase of Saccharomyces cerevisiae, a homotetrameric Mg2+-dependent enzyme that cleaves D-threo-isocitrate into succinate and glyoxylate, the first committed step of the glyoxylate cycle that allows net carbon assimilation from C2 compounds. ICL1 is glucose-repressed and induced on ethanol or acetate (via Cat8p); icl1 null mutants lack isocitrate lyase activity and cannot grow on ethanol or acetate as sole carbon source. Unlike most eukaryotic isocitrate lyases, yeast Icl1p is cytosolic rather than peroxisomal. The enzyme also cleaves 2-methylisocitrate to pyruvate and succinate in vitro. When glucose is replenished after starvation, Icl1p is inactivated and degraded in the vacuole via the Vid pathway.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO (isocitrate lyase/PEP mutase family) mapping to root 'catalytic activity'; uninformative. Reason: Replace with the specific activity. Proposed replacements: isocitrate lyase activity Supporting Evidence: file:yeast/ICL1/ICL1-uniprot.txt Reaction=D-threo-isocitrate = glyoxylate + succinate; |
| GO:0004451 isocitrate lyase activity | EXP PMID:23159490 Lack of Sir2 increases acetate consumption and decreases ext... | ACCEPT | Summary: Orlandi et al. (EXP; abstract-only cache) measured isocitrate lyase activity in a study of Sir2-dependent C2 metabolism; consistent with the established activity. Reason: Deferring to curator; consistent. Supporting Evidence: PMID:23159490 This correlates with an enhanced glyoxylate/gluconeogenic flux which is fuelled by the acetyl-CoA produced from the acetate activation. file:yeast/ICL1/ICL1-uniprot.txt Reaction=D-threo-isocitrate = glyoxylate + succinate; |
| GO:0004451 isocitrate lyase activity | EXP PMID:3059712 Purification of isocitrate lyase from Saccharomyces cerevisi... | ACCEPT | Summary: Lopez-Boado et al. purified Icl1p to homogeneity and characterised its isocitrate lyase kinetics. Reason: Direct biochemical evidence. Supporting Evidence: PMID:3059712 Isocitrate lyase purified to homogeneity from Saccharomyces cerevisiae was composed of four identical subunits with a molecular mass of 75 kDa. PMID:3059712 The Km value for threo-Ds-isocitrate was 1.4 mM. |
| GO:0004451 isocitrate lyase activity | EXP PMID:4259654 Production of pyruvate and succinate by action of isocitrate... | ACCEPT | Summary: McFadden et al. (yeast isocitrate lyase acting on isocitrate and 2-methylisocitrate; abstract not cached) — curator EXP accepted. Reason: Deferring to curator; consistent. Supporting Evidence: file:yeast/ICL1/ICL1-uniprot.txt Reaction=D-threo-isocitrate = glyoxylate + succinate; |
| GO:0004451 isocitrate lyase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA isocitrate lyase activity; Icl1p has direct biochemical evidence. Reason: Core activity. Supporting Evidence: file:yeast/ICL1/ICL1-uniprot.txt Reaction=D-threo-isocitrate = glyoxylate + succinate; PMID:3059712 Isocitrate lyase purified to homogeneity from Saccharomyces cerevisiae was composed of four identical subunits with a molecular mass of 75 kDa. |
| GO:0004451 isocitrate lyase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (InterPro IPR006254, Rhea:13245, EC 4.1.3.1); correct. Reason: Core activity. Supporting Evidence: file:yeast/ICL1/ICL1-uniprot.txt Reaction=D-threo-isocitrate = glyoxylate + succinate; |
| GO:0004451 isocitrate lyase activity | IMP PMID:1551398 The ICL1 gene from Saccharomyces cerevisiae. | ACCEPT | Summary: Fernandez et al.: icl1 deletion abolished isocitrate lyase activity and growth on ethanol. Reason: Genetic evidence. Supporting Evidence: PMID:1551398 It did not have any isocitrate lyase activity and lacked the ability to grow on ethanol as the sole carbon source. |
| GO:0004451 isocitrate lyase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA from the glyoxylate cycle; correct activity in correct pathway. Reason: Correct. Supporting Evidence: file:yeast/ICL1/ICL1-uniprot.txt Reaction=D-threo-isocitrate = glyoxylate + succinate; |
| GO:0004451 isocitrate lyase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA from the TCA/glyoxylate superpathway; activity correct. Reason: Correct activity class. Supporting Evidence: file:yeast/ICL1/ICL1-uniprot.txt Reaction=D-threo-isocitrate = glyoxylate + succinate; |
| GO:0005737 cytoplasm | EXP PMID:20457600 The TOR complex 1 is distributed in endosomes and in retrogr... | ACCEPT | Summary: Brown et al. (EXP): Icl1p is a cytosolic gluconeogenic enzyme that is degraded via Vid vesicles in the vacuole after glucose replenishment. Reason: Experimental location. Supporting Evidence: PMID:20457600 Isocitrate lyase (Icl1p) is a cytosolic protein involved in gluconeogenesis. |
| GO:0005737 cytoplasm | IDA PMID:8870676 Localization and targeting of isocitrate lyases in Saccharom... | ACCEPT | Summary: Taylor et al.: endogenous Icl1p is found solely in cytoplasmic fractions even under peroxisome-inducing conditions. Reason: Experimental location. Supporting Evidence: PMID:8870676 The endogenous S. cerevisiae isocitrate lyase was found solely in the cytoplasmic fractions, even under growth conditions that induce peroxisome proliferation. |
| GO:0005737 cytoplasm | IDA PMID:9370278 Isocitrate lyase localisation in Saccharomyces cerevisiae ce... | ACCEPT | Summary: Chaves et al.: Icl1p localised only in the cytoplasm (fractionation and GFP fusion). Reason: Experimental location. Supporting Evidence: PMID:9370278 The isocitrate lyase from Saccharomyces cerevisiae was only located in the cell cytoplasm. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping to cytoplasm; correct. Reason: Correct. Supporting Evidence: PMID:9370278 The isocitrate lyase from Saccharomyces cerevisiae was only located in the cell cytoplasm. |
| GO:0005773 vacuole | EXP PMID:17651441 Analysis of the vacuolar luminal proteome of Saccharomyces c... | KEEP AS NON CORE | Summary: Sarry et al. vacuolar luminal proteome detected Icl1p; Icl1p reaches the vacuole for degradation (catabolite inactivation), not to function there. Reason: Degradative destination, not a site of activity. Supporting Evidence: PMID:20457600 In this report we show that two additional gluconeogenic enzymes, isocitrate lyase and phosphoenolpyruvate carboxykinase, were also degraded in the vacuole via the Vid pathway. |
| GO:0005773 vacuole | EXP PMID:20457600 The TOR complex 1 is distributed in endosomes and in retrogr... | KEEP AS NON CORE | Summary: Brown et al. (EXP): Icl1p is delivered to the vacuole via the Vid pathway for degradation. Reason: Degradative destination; non-core. Supporting Evidence: PMID:20457600 In this report we show that two additional gluconeogenic enzymes, isocitrate lyase and phosphoenolpyruvate carboxykinase, were also degraded in the vacuole via the Vid pathway. |
| GO:0005773 vacuole | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt subcellular-location mapping to vacuole; reflects degradation route. Reason: Non-core. Supporting Evidence: PMID:20457600 In this report we show that two additional gluconeogenic enzymes, isocitrate lyase and phosphoenolpyruvate carboxykinase, were also degraded in the vacuole via the Vid pathway. |
| GO:0005777 peroxisome | IBA GO_REF:0000033 | REMOVE | Summary: PAINT IBA is_active_in peroxisome (PTN001091863) inherited from plant/fungal peroxisomal isocitrate lyases. Yeast Icl1p lacks peroxisomal localisation even under peroxisome-proliferating conditions and is the documented exception in the family. Reason: Target-specific evidence contradicts the inherited location. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN001091863 SUPPORTS SOURCE BUT NOT TARGET Peroxisomal location holds for plant/filamentous-fungal isocitrate lyases but S. cerevisiae Icl1p is cytosolic and lacks a PTS. Supporting Evidence: PMID:8870676 The endogenous S. cerevisiae isocitrate lyase was found solely in the cytoplasmic fractions, even under growth conditions that induce peroxisome proliferation. PMID:9370278 The isocitrate lyase from Saccharomyces cerevisiae was only located in the cell cytoplasm. file:yeast/ICL1/ICL1-uniprot.txt MISCELLANEOUS: Yeast isocitrate lyase is the only eukaryotic member of |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA is_active_in cytosol for the glyoxylate cycle; matches experimental localisation. Reason: Correct. Supporting Evidence: PMID:9370278 The isocitrate lyase from Saccharomyces cerevisiae was only located in the cell cytoplasm. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA is_active_in cytosol for the superpathway; correct. Reason: Correct. Supporting Evidence: PMID:9370278 The isocitrate lyase from Saccharomyces cerevisiae was only located in the cell cytoplasm. |
| GO:0006097 glyoxylate cycle | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA glyoxylate cycle; Icl1p is the yeast glyoxylate-cycle isocitrate lyase. Reason: Core process. Supporting Evidence: PMID:1551398 It did not have any isocitrate lyase activity and lacked the ability to grow on ethanol as the sole carbon source. PMID:8870676 This result shows that the presence of isocitrate lyase in peroxisomes is not essential for a functional glyoxylate cycle. |
| GO:0006097 glyoxylate cycle | IEA GO_REF:0000041 | ACCEPT | Summary: UniPathway IEA (UPA00703) glyoxylate cycle; correct. Reason: Core process. Supporting Evidence: PMID:8870676 This result shows that the presence of isocitrate lyase in peroxisomes is not essential for a functional glyoxylate cycle. |
| GO:0006097 glyoxylate cycle | IMP PMID:8878673 Mutants of Saccharomyces cerevisiae with defects in acetate ... | ACCEPT | Summary: McCammon isolated acetate non-utilising (acn) mutants; ICL1 was among the glyoxylate-cycle genes required for acetate growth. Reason: Genetic evidence. Supporting Evidence: PMID:8878673 Four genes encode enzymes of the glyoxylate cycle and gluconeogenesis: ICL1, MLS1, MDH2, and PCK1. |
| GO:0006097 glyoxylate cycle | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA glyoxylate cycle; correct. Reason: Core process. Supporting Evidence: PMID:8870676 This result shows that the presence of isocitrate lyase in peroxisomes is not essential for a functional glyoxylate cycle. |
| GO:0032787 monocarboxylic acid metabolic process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: ARBA IEA for 'monocarboxylic acid metabolic process'. Isocitrate, glyoxylate and succinate are not the focus of this grouping; the informative process is glyoxylate cycle. Reason: Vague, not informative. Supporting Evidence: file:yeast/ICL1/ICL1-uniprot.txt Reaction=D-threo-isocitrate = glyoxylate + succinate; |
| GO:0046421 methylisocitrate lyase activity | EXP PMID:3059712 Purification of isocitrate lyase from Saccharomyces cerevisi... | KEEP AS NON CORE | Summary: Lopez-Boado et al. (EXP) — UniProt attributes methylisocitrate lyase activity (EC 4.1.3.30) to purified yeast isocitrate lyase. Physiological relevance for propionate catabolism by cytosolic Icl1p has not been shown. Reason: Real in vitro side activity; not the physiological role. Supporting Evidence: file:yeast/ICL1/ICL1-uniprot.txt Reaction=(2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate = pyruvate + |
| GO:0046421 methylisocitrate lyase activity | EXP PMID:4259654 Production of pyruvate and succinate by action of isocitrate... | KEEP AS NON CORE | Summary: McFadden et al.: yeast isocitrate lyase cleaves 2-methylisocitrate to pyruvate and succinate (title of the paper). In vitro substrate promiscuity. Reason: In vitro side activity; non-core. Supporting Evidence: file:yeast/ICL1/ICL1-uniprot.txt Reaction=(2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate = pyruvate + |
| GO:0046421 methylisocitrate lyase activity | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Combined IEA (ARBA, Rhea:16809, EC 4.1.3.30) methylisocitrate lyase activity; consistent with in vitro data but not the physiological activity. Reason: Non-core. Supporting Evidence: file:yeast/ICL1/ICL1-uniprot.txt Reaction=(2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate = pyruvate + |
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