Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005739 mitochondrion	HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen...	ACCEPT	Summary: Mitochondrial proteome (Reinders et al. 2006) detected Cit3p. Reason: Correct location. Supporting Evidence: PMID:9140965 In vitro import experiments showed that cit3p is transported into the mitochondria.
GO:0005739 mitochondrion	HDA PMID:24769239 Quantitative variations of the mitochondrial proteome and ph...	ACCEPT	Summary: Quantitative mitochondrial proteome (Renvoise et al. 2014) detected Cit3p. Reason: Correct location. Supporting Evidence: PMID:9140965 In vitro import experiments showed that cit3p is transported into the mitochondria.
GO:0005739 mitochondrion	IDA PMID:9140965 The CIT3 gene of Saccharomyces cerevisiae encodes a second m...	ACCEPT	Summary: Jia et al. showed in vitro import of Cit3p into mitochondria. Reason: Direct evidence. Supporting Evidence: PMID:9140965 In vitro import experiments showed that cit3p is transported into the mitochondria.
GO:0005739 mitochondrion	IEA GO_REF:0000044	ACCEPT	Summary: UniProt subcellular-location mapping to mitochondrion; correct. Reason: Correct location. Supporting Evidence: PMID:9140965 In vitro import experiments showed that cit3p is transported into the mitochondria.
GO:0005739 mitochondrion	RCA GO_REF:0000123	ACCEPT	Summary: YeastPathways RCA is_active_in mitochondrion from TCA-EUK-PWY; correct. Reason: Correct location. Supporting Evidence: PMID:9140965 In vitro import experiments showed that cit3p is transported into the mitochondria.
GO:0005759 mitochondrial matrix	IBA GO_REF:0000033	ACCEPT	Summary: PAINT IBA is_active_in mitochondrial matrix for the mitochondrial citrate synthase clade; Cit3p is imported and acts in the matrix with Cit1p. Reason: Correct inherited location. Supporting Evidence: PMID:9140965 In vitro import experiments showed that cit3p is transported into the mitochondria.
GO:0005829 cytosol	RCA GO_REF:0000123	REMOVE	Summary: YeastPathways RCA is_active_in cytosol inherited from the TCA/glyoxylate superpathway (PWY3O-94). Cit3p is mitochondrial; the extramitochondrial isozyme is Cit2p. Reason: Superpathway/paralog artefact; wrong compartment. Supporting Evidence: PMID:9140965 In vitro import experiments showed that cit3p is transported into the mitochondria.
GO:0005975 carbohydrate metabolic process	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: PAINT IBA carbohydrate metabolic process; vague grouping adding nothing beyond TCA cycle/propionate catabolism. 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: file:yeast/CIT3/CIT3-uniprot.txt FUNCTION: Dual specificity mitochondrial citrate and methylcitrate
GO:0006099 tricarboxylic acid cycle	IBA GO_REF:0000033	ACCEPT	Summary: PAINT IBA tricarboxylic acid cycle; Cit3p is a functional mitochondrial citrate synthase that supports respiratory growth in the absence of Cit1p. Reason: Correct process. Supporting Evidence: PMID:9140965 Deletion of the CIT3 gene in a delta cit1 background severely reduced growth on the respiratory substrate glycerol
GO:0006099 tricarboxylic acid cycle	IDA PMID:17570335 Functional comparison of citrate synthase isoforms from S. c...	ACCEPT	Summary: Graybill et al. (abstract-only cache): Cit3p has citrate synthase activity comparable to its methylcitrate synthase activity; curator IDA for TCA cycle accepted. Reason: Deferring to curator; consistent with biochemistry. 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:0006099 tricarboxylic acid cycle	IEA GO_REF:0000041	ACCEPT	Summary: UniPathway-based IEA (UPA00223) TCA cycle; correct. Reason: Correct process. Supporting Evidence: PMID:9140965 Deletion of the CIT3 gene in a delta cit1 background severely reduced growth on the respiratory substrate glycerol
GO:0009060 aerobic respiration	RCA GO_REF:0000123	KEEP AS NON CORE	Summary: YeastPathways RCA aerobic respiration from TCA-EUK-PWY; correct parent but less specific than TCA cycle. Reason: Correct but general. Supporting Evidence: PMID:9140965 Deletion of the CIT3 gene in a delta cit1 background severely reduced growth on the respiratory substrate glycerol
GO:0019543 propionate catabolic process	IGI PMID:17570335 Functional comparison of citrate synthase isoforms from S. c...	ACCEPT	Summary: Graybill et al.: cit2 cit3 double mutant fails to grow on propionate and cit3 cells fail to convert 13C-propionate to pyruvate/alanine; Cit3p catalyses the methylcitrate synthase step of propionate catabolism. Reason: Experimental support; Cit3p performs the first step of the methylcitrate cycle. Supporting Evidence: PMID:17570335 The Deltacit2Deltacit3 double mutant did not grow on propionate, providing further evidence for the role of Cit3p in propionate metabolism. PMID:17570335 (13)C NMR analysis showed the metabolism of 2-(13)C-propionate to acetate, pyruvate, and alanine in wild-type, Deltacit1 and Deltacit2 cells, but not in the Deltacit3 mutant.
GO:0036440 citrate synthase activity	IBA GO_REF:0000033	ACCEPT	Summary: PAINT IBA citrate synthase activity; Cit3p is an active citrate synthase. Reason: Core activity. Supporting Evidence: PMID:9140965 Complementation of a citrate synthase-deficient strain of Escherichia coli by lacZ::CIT3 gene fusions demonstrated that the CIT3 gene encodes an active citrate synthase.
GO:0036440 citrate synthase activity	IDA PMID:17570335 Functional comparison of citrate synthase isoforms from S. c...	ACCEPT	Summary: Graybill et al.: recombinant Cit3p is active with acetyl-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 (ARBA, Rhea:16845, EC 2.3.3.1); correct. Reason: Core activity. Supporting Evidence: file:yeast/CIT3/CIT3-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. (abstract-only cache) IMP; consistent with Cit3p being an active citrate synthase whose deletion affects respiratory growth in cit1 backgrounds. Reason: Consistent. Supporting Evidence: PMID:9140965 Deletion of the CIT3 gene in a delta cit1 background severely reduced growth on the respiratory substrate glycerol
GO:0036440 citrate synthase activity	RCA GO_REF:0000123	ACCEPT	Summary: YeastPathways RCA superpathway; activity class correct (compartment issue handled on CC row). Reason: Correct activity class. Supporting Evidence: file:yeast/CIT3/CIT3-uniprot.txt Reaction=oxaloacetate + acetyl-CoA + H2O = citrate + CoA + H(+);
GO:0036440 citrate synthase activity	RCA GO_REF:0000123	ACCEPT	Summary: YeastPathways RCA TCA cycle; correct. Reason: Correct activity. Supporting Evidence: file:yeast/CIT3/CIT3-uniprot.txt Reaction=oxaloacetate + acetyl-CoA + H2O = citrate + CoA + H(+);
GO:0046912 acyltransferase activity, acyl groups converted into alkyl on transfer	IEA GO_REF:0000002	MODIFY	Summary: InterPro2GO mapping to the EC 2.3.3 parent 'acyltransferase activity, acyl groups converted into alkyl on transfer'; correct but uninformative. Reason: Replace with specific activities. Proposed replacements: citrate synthase activity 2-methylcitrate synthase activity Supporting Evidence: file:yeast/CIT3/CIT3-uniprot.txt Reaction=oxaloacetate + acetyl-CoA + H2O = citrate + CoA + H(+);
GO:0050440 2-methylcitrate synthase activity	IBA GO_REF:0000033	ACCEPT	Summary: PAINT IBA 2-methylcitrate synthase activity (PTN000746749); Cit3p has direct evidence for this dual specificity, so the inherited assignment is grounded. 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.
GO:0050440 2-methylcitrate synthase activity	IDA PMID:17570335 Functional comparison of citrate synthase isoforms from S. c...	ACCEPT	Summary: Graybill et al.: recombinant Cit3p uses propionyl-CoA with similar efficiency to acetyl-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. PMID:17570335 the product of the CIT3 gene has been identified as a dual specificity mitochondrial citrate and methylcitrate synthase and that of the CIT1 gene as a specific citrate synthase
GO:0050440 2-methylcitrate synthase activity	IEA GO_REF:0000117	ACCEPT	Summary: ARBA machine-learning IEA for 2-methylcitrate synthase activity; correct for Cit3p. Reason: Correct. 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:0050440 2-methylcitrate synthase activity	IMP PMID:17570335 Functional comparison of citrate synthase isoforms from S. c...	ACCEPT	Summary: Graybill et al.: cit2 cit3 double mutant lacks all methylcitrate synthase activity. Reason: Genetic evidence. Supporting Evidence: PMID:17570335 A Deltacit2Deltacit3 strain showed no methylcitrate synthase activity, suggesting that Cit2p, a peroxisomal isoform, may also have methylcitrate synthase activity.

Core Functions

Mitochondrial 2-methylcitrate synthase condensing propionyl-CoA with oxaloacetate, the first step of the methylcitrate cycle for propionate (propionyl-CoA) catabolism to pyruvate.

Molecular Function:

2-methylcitrate synthase activity

Directly Involved In:

propionate catabolic process

Cellular Locations:

mitochondrial matrix

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.
PMID:17570335
The Deltacit2Deltacit3 double mutant did not grow on propionate, providing further evidence for the role of Cit3p in propionate metabolism.
PMID:17570335
(13)C NMR analysis showed the metabolism of 2-(13)C-propionate to acetate, pyruvate, and alanine in wild-type, Deltacit1 and Deltacit2 cells, but not in the Deltacit3 mutant.

Minor mitochondrial citrate synthase that backs up Cit1p in the TCA cycle.

Molecular Function:

citrate synthase activity

Directly Involved In:

tricarboxylic acid cycle

Cellular Locations:

mitochondrial matrix

Supporting Evidence:

PMID:9140965
Deletion of the CIT3 gene in a delta cit1 background severely reduced growth on the respiratory substrate glycerol
PMID:9140965
Complementation of a citrate synthase-deficient strain of Escherichia coli by lacZ::CIT3 gene fusions demonstrated that the CIT3 gene encodes an active citrate synthase.
PMID:17570335
Recombinant Cit1p had catalytic activity only with acetyl-CoA whereas Cit3p had similar catalytic efficiency with both acetyl-CoA and propionyl-CoA.

References

Loading supporting content…

Download this section (compressed HTML)

Deep Research

SGD

(CIT3-deep-research-sgd.md)

SGD gene description for CIT3 (yeast) SGD

SGD gene description for CIT3 (yeast)

Dual specificity mitochondrial citrate and methylcitrate synthase; catalyzes the condensation of acetyl-CoA and oxaloacetate to form citrate and that of propionyl-CoA and oxaloacetate to form 2-methylcitrate

📚 Additional Documentation

Notes

(CIT3-notes.md)

CIT3 (YPR001W, P43635) notes

Third citrate synthase; imported into mitochondria; cit1 cit3 poor growth on glycerol PMID:9140965.
Dual citrate/2-methylcitrate synthase PMID:17570335; required for propionate metabolism PMID:17570335.
cit3 accumulates acetate and isobutanol (propionyl-CoA inhibition of PDH proposed) [UniProt:P43635].

Curation: YeastCyc superpathway cytosol row removed. Core: 2-methylcitrate synthase in propionate catabolism (methylcitrate cycle) + backup TCA citrate synthase.

📄 View Raw YAML