CIT1 encodes the major mitochondrial citrate synthase of Saccharomyces cerevisiae, which condenses acetyl-CoA with oxaloacetate to form citrate in the mitochondrial matrix, the first committed step of the tricarboxylic acid cycle. Unlike its paralog CIT3, Cit1p is specific for acetyl-CoA and has no methylcitrate synthase activity. It is active as a homodimer; phosphorylation of Ser462 blocks dimerisation and activity and is reversed by the matrix phosphatase Ptc7p. Deletion of CIT1 impairs respiratory metabolism and growth on acetate, and a cit1 cit2 double mutant is a glutamate auxotroph. Cit1p has been found in a supramolecular association with other matrix dehydrogenases and TCA-cycle enzymes. CIT1 transcription is subject to glucose repression and is further repressed by glutamate; its derepression on non-fermentable carbon sources requires the Hap2/3/4 transcriptional activator, which coordinates it with expression of respiratory chain genes.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005739 mitochondrion | HDA PMID:11914276 Subcellular localization of the yeast proteome. | ACCEPT | Summary: Genome-wide subcellular proteomics (Kumar et al. 2002) placed Cit1p in mitochondria. Reason: Correct location. Supporting Evidence: file:yeast/CIT1/CIT1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005739 mitochondrion | HDA PMID:14576278 The proteome of Saccharomyces cerevisiae mitochondria. | ACCEPT | Summary: Mitochondrial proteome (Sickmann et al. 2003) detected Cit1p. Reason: Correct location. Supporting Evidence: file:yeast/CIT1/CIT1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | ACCEPT | Summary: Mitochondrial proteome (Reinders et al. 2006) detected Cit1p. Reason: Correct location. Supporting Evidence: file:yeast/CIT1/CIT1-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 Cit1p. Reason: Correct location. Supporting Evidence: file:yeast/CIT1/CIT1-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 Cit1p in a mitochondrial supramolecular dehydrogenase complex isolated by native PAGE. Reason: Direct observation in mitochondria. 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 | IPI PMID:16962558 Enolase takes part in a macromolecular complex associated to... | ACCEPT | Summary: Brandina et al. (enolase-mitochondria association study, abstract-only cache) — curator recorded Cit1p in a mitochondrion-associated complex; consistent with its known location. Reason: Deferring to curator; consistent with established location. Supporting Evidence: file:yeast/CIT1/CIT1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005739 mitochondrion | IPI PMID:16962558 Enolase takes part in a macromolecular complex associated to... | ACCEPT | Summary: Duplicate row from PMID:16962558 (different with/from partner); mitochondrial location is correct for Cit1p. Reason: Consistent with established location. Supporting Evidence: file:yeast/CIT1/CIT1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005739 mitochondrion | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA is_active_in mitochondrion from the TCA cycle pathway; correct for Cit1p. Reason: Correct location. Supporting Evidence: file:yeast/CIT1/CIT1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005758 mitochondrial intermembrane space | TAS Reactome:R-SCE-1252255 | REMOVE | Summary: Reactome TAS from the TOM40:TOM70 import reaction (computationally projected), in which Cit1p is a translocating cargo. Cit1p is a matrix enzyme, not an intermembrane-space resident. Reason: Transit step of import mis-read as a location. Supporting Evidence: file:yeast/CIT1/CIT1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005759 mitochondrial matrix | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA is_active_in mitochondrial matrix for the mitochondrial citrate synthase clade; correct for Cit1p. Reason: Correct location. Supporting Evidence: file:yeast/CIT1/CIT1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005759 mitochondrial matrix | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location mapping to mitochondrial matrix; correct. Reason: Correct location. Supporting Evidence: file:yeast/CIT1/CIT1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: YeastPathways RCA is_active_in cytosol inherited from the TCA/glyoxylate superpathway (PWY3O-94), where the cytosolic/peroxisomal citrate synthase is Cit2p. Cit1p is a matrix enzyme with no evidence of a cytosolic pool. Reason: Superpathway/paralog artefact; wrong compartment for Cit1p. Supporting Evidence: file:yeast/CIT1/CIT1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005829 cytosol | TAS Reactome:R-SCE-1252255 | REMOVE | Summary: Reactome TAS cytosol from the TOM40:TOM70 import reaction (Cit1p as precursor in transit); not a resident location. Reason: Transit step mis-read as location. Supporting Evidence: file:yeast/CIT1/CIT1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005975 carbohydrate metabolic process | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: PAINT IBA for carbohydrate metabolic process on the citrate synthase node. Citrate synthase acts in the TCA cycle; 'carbohydrate metabolic process' is a vague grouping that adds nothing beyond the TCA-cycle annotation. Reason: Uninformative over-general process. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000201223 SUPPORTS TRANSFER Node-level grouping term; vague rather than wrong. Supporting Evidence: PMID:28076776 Cit1p, the canonical citrate synthase of the tricarboxylic acid (TCA) cycle |
| GO:0006099 tricarboxylic acid cycle | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for tricarboxylic acid cycle; Cit1p is the canonical TCA citrate synthase with its own experimental support. Reason: Core process. Supporting Evidence: PMID:28076776 Cit1p, the canonical citrate synthase of the tricarboxylic acid (TCA) cycle |
| GO:0006099 tricarboxylic acid cycle | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (InterPro IPR010109, UniPathway UPA00223) for TCA cycle; correct. Reason: Core process. Supporting Evidence: PMID:28076776 Cit1p, the canonical citrate synthase of the tricarboxylic acid (TCA) cycle |
| GO:0006099 tricarboxylic acid cycle | IMP PMID:2661555 Metabolic studies on citrate synthase mutants of yeast. A ch... | ACCEPT | Summary: Kispal et al.: deletion of mitochondrial citrate synthase reduced mitochondrial respiration of citrate/isocitrate and prevented growth on acetate. Reason: Mutant phenotype supports TCA role. Supporting Evidence: PMID:2661555 Deletion of mitochondrial citrate synthase (CS1) protein resulted in changes in metabolites PMID:2661555 reduced mitochondrial respiration of citrate and isocitrate, and an inability to grow on acetate |
| GO:0006101 citrate metabolic process | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Combined IEA (ARBA, InterPro) for citrate metabolic process; true (citrate is the product) but less informative than TCA cycle. Reason: Correct but general. Supporting Evidence: file:yeast/CIT1/CIT1-uniprot.txt Reaction=oxaloacetate + acetyl-CoA + H2O = citrate + CoA + H(+); |
| GO:0006101 citrate metabolic process | IGI PMID:12913175 Modulation of citrate metabolism alters aluminum tolerance i... | KEEP AS NON CORE | Summary: Anoop et al.: CS mutants accumulate less citrate and CIT1 overexpression raises citrate levels (aluminium-tolerance study). Supports a role in citrate production. Reason: Correct but general relative to TCA cycle. Supporting Evidence: PMID:12913175 A triple mutant of CS (Deltacit123) showed lower levels of citrate accumulation and reduced Al tolerance PMID:12913175 Overexpression of a mitochondrial CS (CIT1) in MMYO11 resulted in a 2- to 3-fold increase in citrate levels |
| GO:0006101 citrate metabolic process | IGI PMID:12913175 Modulation of citrate metabolism alters aluminum tolerance i... | KEEP AS NON CORE | Summary: Second IGI row from PMID:12913175 (different interacting gene); same evidence that citrate synthase mutants alter cellular citrate. Reason: Correct but general. Supporting Evidence: PMID:12913175 A triple mutant of CS (Deltacit123) showed lower levels of citrate accumulation and reduced Al tolerance |
| GO:0009060 aerobic respiration | RCA GO_REF:0000123 | KEEP AS NON CORE | Summary: YeastPathways RCA aerobic respiration from TCA-EUK-PWY; correct parent of the TCA cycle but less specific. Reason: Correct but general. Supporting Evidence: PMID:28076776 Cit1p, the canonical citrate synthase of the tricarboxylic acid (TCA) cycle |
| GO:0036440 citrate synthase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA citrate synthase activity; Cit1p has extensive direct biochemical evidence. Reason: Core activity. Supporting Evidence: PMID:17570335 Recombinant Cit1p had catalytic activity only with acetyl-CoA whereas Cit3p had similar catalytic efficiency with both acetyl-CoA and propionyl-CoA. file:yeast/CIT1/CIT1-uniprot.txt Reaction=oxaloacetate + acetyl-CoA + H2O = citrate + CoA + H(+); |
| GO:0036440 citrate synthase activity | IDA PMID:17570335 Functional comparison of citrate synthase isoforms from S. c... | ACCEPT | Summary: Graybill et al.: recombinant Cit1p catalyses citrate synthesis with acetyl-CoA (not propionyl-CoA). Reason: Direct assay. Supporting Evidence: PMID:17570335 Recombinant Cit1p had catalytic activity only with acetyl-CoA whereas Cit3p had similar catalytic efficiency with both acetyl-CoA and propionyl-CoA. |
| GO:0036440 citrate synthase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (Rhea:16845, EC 2.3.3.1); correct. Reason: Core activity. Supporting Evidence: file:yeast/CIT1/CIT1-uniprot.txt Reaction=oxaloacetate + acetyl-CoA + H2O = citrate + CoA + H(+); |
| GO:0036440 citrate synthase activity | IMP PMID:17570335 Functional comparison of citrate synthase isoforms from S. c... | ACCEPT | Summary: Graybill et al.: deletion of CIT1 removes most cellular citrate synthase activity, shifting extracts toward methylcitrate synthase. Reason: Mutant phenotype consistent. Supporting Evidence: PMID:17570335 Deletion of CIT1 dramatically shifted the ratio of these two activities in whole cell extracts towards greater methylcitrate synthase. |
| GO:0036440 citrate synthase activity | IMP PMID:2661555 Metabolic studies on citrate synthase mutants of yeast. A ch... | ACCEPT | Summary: Kispal et al.: active-site mutants (H313G, D414G) of CS1 give inactive protein in mitochondria, confirming Cit1p is the catalytically active enzyme. Reason: Mutational evidence for the activity. Supporting Evidence: PMID:2661555 Deletion of mitochondrial citrate synthase (CS1) protein resulted in changes in metabolites |
| GO:0036440 citrate synthase activity | IMP PMID:28076776 Ptc7p Dephosphorylates Select Mitochondrial Proteins to Enha... | ACCEPT | Summary: Guo et al.: phosphorylation of Ser462 abolishes Cit1p activity and Ptc7p dephosphorylation restores it. Reason: Experimental evidence. Supporting Evidence: PMID:28076776 We find that phosphorylation of S462 can eliminate Cit1p enzymatic activity likely by disrupting its proper dimerization, and that Ptc7p-driven dephosphorylation rescues Cit1p activity. |
| GO:0036440 citrate synthase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA from the TCA/glyoxylate superpathway (PWY3O-94); activity correct (compartment issues are handled on the CC rows). Reason: Correct activity class. Supporting Evidence: file:yeast/CIT1/CIT1-uniprot.txt Reaction=oxaloacetate + acetyl-CoA + H2O = citrate + CoA + H(+); |
| GO:0036440 citrate synthase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA from the TCA cycle (TCA-EUK-PWY); correct. Reason: Correct activity in correct pathway. Supporting Evidence: file:yeast/CIT1/CIT1-uniprot.txt Reaction=oxaloacetate + acetyl-CoA + H2O = citrate + CoA + H(+); |
| GO:0046356 acetyl-CoA catabolic process | IDA PMID:17570335 Functional comparison of citrate synthase isoforms from S. c... | KEEP AS NON CORE | Summary: Graybill et al. (abstract-only cache) — acetyl-CoA catabolic process inferred because Cit1p consumes acetyl-CoA. True in the sense that the TCA cycle oxidises acetyl-CoA, but adds little beyond the TCA-cycle annotation. Reason: Correct but redundant with TCA cycle. Supporting Evidence: PMID:17570335 Recombinant Cit1p had catalytic activity only with acetyl-CoA whereas Cit3p had similar catalytic efficiency with both acetyl-CoA and propionyl-CoA. |
| GO:0046356 acetyl-CoA catabolic process | IMP PMID:17570335 Functional comparison of citrate synthase isoforms from S. c... | KEEP AS NON CORE | Summary: IMP companion of the acetyl-CoA catabolic process row (PMID:17570335). Reason: Correct but redundant with TCA cycle. Supporting Evidence: PMID:17570335 Deletion of CIT1 dramatically shifted the ratio of these two activities in whole cell extracts towards greater methylcitrate synthase. |
| GO:0046912 acyltransferase activity, acyl groups converted into alkyl on transfer | IEA GO_REF:0000120 | MODIFY | Summary: Combined IEA (ARBA, InterPro citrate synthase domains) for 'acyltransferase activity, acyl groups converted into alkyl on transfer' — the EC 2.3.3 parent of citrate synthase. Correct but uninformative. Reason: Replace with the specific activity. Proposed replacements: citrate synthase activity Supporting Evidence: file:yeast/CIT1/CIT1-uniprot.txt Reaction=oxaloacetate + acetyl-CoA + H2O = citrate + CoA + H(+); |
Loading supporting content…
Download this section (compressed HTML)Mitochondrial citrate synthase; catalyzes condensation of acetyl coenzyme A and oxaloacetate to form citrate, which is the first and rate-limiting step of the TCA cycle; transcription subject to glucose repression; CIT1 has a paralog, CIT2, that arose from the whole genome duplication
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)