CAT2

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004092 carnitine O-acetyltransferase activity	IBA GO_REF:0000033	ACCEPT	Summary: Carnitine O-acetyltransferase activity is the primary and well-established enzymatic function of CAT2. This is supported by phylogenetic inference (IBA) from orthologous proteins and backed by direct experimental evidence (IMP from PMID:8420957). The UniProt record explicitly states the catalytic activity: (R)-carnitine + acetyl-CoA = O-acetyl-(R)-carnitine + CoA (EC 2.3.1.7). The term appropriately represents the core molecular function of this enzyme. Supporting Evidence: PMID:8420957 This cDNA was used successfully to disrupt the gene for the mitochondrial isoenzyme of CAT, which was shown by measuring the enzyme activity and by immunoblot [Establishes enzymatic activity] file:yeast/CAT2/CAT2-deep-research-falcon.md reversible transfer of acetyl groups between acetyl-CoA and L-carnitine file:yeast/CAT2/CAT2-deep-research-falcon.md ~95% of total carnitine acetyltransferase activity in oleate-grown cells
GO:0005739 mitochondrion	IBA GO_REF:0000033	ACCEPT	Summary: CAT2 localizes to mitochondria, specifically as a mitochondrial isoform at the inner mitochondrial membrane. This is supported by phylogenetic inference (IBA) and confirmed by direct experimental evidence (IDA from PMID:18427809 and PMID:25372298). The UniProt record explicitly documents the mitochondrial localization of the primary isoform. Supporting Evidence: PMID:18427809 Carnitine and carnitine acetyltransferases in the yeast Saccharomyces cerevisiae: a role for carnitine in stress protection file:yeast/CAT2/CAT2-deep-research-falcon.md dually localized to peroxisomes and mitochondria
GO:0005777 peroxisome	IBA GO_REF:0000033	ACCEPT	Summary: CAT2 localizes to peroxisomes as a second isoform derived from alternative initiation. This is supported by phylogenetic inference (IBA) and confirmed by direct experimental evidence (IDA from PMID:18427809, PMID:22375831). The UniProt record documents that the peroxisomal isoform is produced by alternative initiation at Met-23 and contains a C-terminal peroxisomal targeting signal (SKL). Supporting Evidence: PMID:18427809 Carnitine and carnitine acetyltransferases in the yeast Saccharomyces cerevisiae: a role for carnitine in stress protection file:yeast/CAT2/CAT2-deep-research-falcon.md two ATG codons can produce isoforms, one containing an N-terminal mitochondrial targeting signal, while a C-terminal PTS1 (AKL)** provides peroxisomal targeting potential file:yeast/CAT2/CAT2-deep-research-falcon.md Cat2 with an N-terminal fluorescent tag showed punctate/peroxisomal localization
GO:0009437 carnitine metabolic process	IBA GO_REF:0000033	ACCEPT	Summary: CAT2 is essential for carnitine-dependent metabolic processes. This is supported by phylogenetic inference (IBA) and strong experimental evidence (IMP from PMID:11329169). The enzyme catalyzes the reversible acetylation of carnitine, which is the central reaction in the carnitine shuttle for transferring acetyl groups across organellar membranes. Supporting Evidence: PMID:11329169 Carnitine-dependent metabolic activities in Saccharomyces cerevisiae: three carnitine acetyltransferases are essential in a carnitine-dependent strain file:yeast/CAT2/CAT2-deep-research-falcon.md Cat2p is the principal enzymatic component of the yeast carnitine shuttle for acetyl-unit transfer between organelles
GO:0004092 carnitine O-acetyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: This is a computational annotation from combined automated annotation methods (IEA from GO_REF:0000120). It represents the same core function as the IBA and IMP annotations, supported by EC classification 2.3.1.7 and RHEA reaction mapping. This annotation is redundant with the higher-quality IBA and IMP evidence but provides additional confirmation of the enzymatic function.
GO:0005743 mitochondrial inner membrane	IEA GO_REF:0000044	ACCEPT	Summary: This annotation specifies the precise mitochondrial localization of CAT2 (mitochondrial isoform). This is a computational annotation derived from UniProtKB subcellular location vocabulary mapping (GO_REF:0000044) and is accurate. The UniProt record explicitly states the primary isoform localizes to the mitochondrial inner membrane as a peripheral membrane protein. The term is appropriately specific and supported by the documented isoform structure.
GO:0005777 peroxisome	IEA GO_REF:0000044	ACCEPT	Summary: This is a computational annotation from UniProtKB subcellular location vocabulary mapping (GO_REF:0000044) documenting the peroxisomal localization of the CAT2 peroxisomal isoform. This is accurate and supported by direct experimental evidence (IDA from PMID:18427809, PMID:22375831). The annotation appropriately represents the documented alternative isoform.
GO:0006629 lipid metabolic process	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: This annotation is derived from UniProtKB keyword mapping (GO_REF:0000043, KW-0443: Lipid metabolism). CAT2 is involved in lipid metabolism through its role in the carnitine shuttle for fatty acid oxidation in peroxisomes. However, this is an indirect and broad annotation. While not incorrect, the more specific process term "carnitine-dependent fatty acid oxidation" or "fatty acid metabolic process" would be more informative. Reason: This term is accurate but overly general. CAT2 contributes to lipid metabolism through the carnitine shuttle facilitating fatty acid oxidation, but this is a secondary effect of its primary function. The term represents a higher-level process that encompasses the more specific functions already captured by GO:0006631 (fatty acid metabolic process) and GO:0009437 (carnitine metabolic process).
GO:0006631 fatty acid metabolic process	IEA GO_REF:0000043	ACCEPT	Summary: This annotation is derived from UniProtKB keyword mapping (GO_REF:0000043, KW-0276: Fatty acid metabolism). CAT2 is directly involved in fatty acid oxidation through the carnitine shuttle mechanism. In yeast, peroxisomes are the primary site of fatty acid oxidation, and CAT2 is essential for this process by facilitating the transport of acetyl groups from peroxisomes to mitochondria. This is supported by PMID:11329169, which documents the essential role of all three CAT enzymes in carnitine-dependent fatty acid metabolism. Supporting Evidence: PMID:11329169 L-carnitine and all three CATs are essential for growth on non-fermentable carbon sources in a strain with a disrupted CIT2 gene [Documents CAT2 role in fatty acid metabolism] file:yeast/CAT2/CAT2-deep-research-falcon.md loss of both systems (e.g., Δcit2 Δcat2) abolishes growth on fatty acids such as oleate file:yeast/CAT2/CAT2-deep-research-falcon.md in a cit2-disrupted background, L-carnitine and carnitine acetyltransferases become essential for growth on non-fermentable carbon sources
GO:0016740 transferase activity	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: This annotation is derived from UniProtKB keyword mapping (GO_REF:0000043, KW-0808: Transferase). CAT2 is indeed a transferase, catalyzing the transfer of acetyl groups from acetyl-CoA to carnitine. However, this is a very broad and general molecular function term. The specific function is much better represented by GO:0004092 (carnitine O-acetyltransferase activity) and GO:0016746 (acyltransferase activity), which provide more informative classification. Reason: While technically correct, this term is too general and uninformative. GO:0004092 provides the specific enzymatic classification, and this broader term adds little additional value. It represents a parent term of the more specific acyltransferase activity.
GO:0016746 acyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: This annotation is derived from automated annotation methods (GO_REF:0000120) mapping InterPro domain IPR000542 (Carnitine/choline acetyltransferase family). CAT2 is indeed an acyltransferase, specifically catalyzing the transfer of an acetyl group (an acyl group) from acetyl-CoA to carnitine. This is a reasonable intermediate-level classification between the general transferase activity and the specific carnitine O-acetyltransferase activity.
GO:0005515 protein binding	IPI PMID:27107014 An inter-species protein-protein interaction network across ...	MARK AS OVER ANNOTATED	Summary: This annotation is from a protein-protein interaction study (IPI, PMID:27107014), documenting interaction with a human ortholog (UniProtKB:Q9H190). While this indicates CAT2 has protein binding capability, the term "protein binding" is non-specific and uninformative. Every protein binds to other molecules; this does not distinguish the biological function. Without knowledge of the specific interaction partner or functional consequence, this annotation provides minimal functional insight. Reason: The term "protein binding" is too vague and generic. This annotation documents a protein-protein interaction from an inter-species study, but provides no functional context. The interaction partner appears to be a human ortholog used for comparative analysis rather than a specific yeast interaction. More informative would be specific binding partner information or functional roles (e.g., substrate/product binding). This annotation does not represent a core biological function of the enzyme. Supporting Evidence: PMID:27107014 An inter-species protein-protein interaction network across vast evolutionary distance.
GO:0005777 peroxisome	IDA PMID:22375831 Identification of core components and transient interactors ...	ACCEPT	Summary: This annotation documents peroxisomal localization based on direct evidence (IDA). PMID:22375831 is a proteomics study of the peroxisomal importomer that identified CAT2 as a component or interactor in peroxisomal protein import machinery. This provides direct evidence for peroxisomal localization. The annotation is accurate and supported by the experimental approach. Supporting Evidence: PMID:22375831 Identification of core components and transient interactors of the peroxisomal importomer by dual-track stable isotope labeling with amino acids in cell culture analysis [Direct identification in peroxisomal protein import studies]
GO:0005739 mitochondrion	HDA PMID:24769239 Quantitative variations of the mitochondrial proteome and ph...	ACCEPT	Summary: This annotation documents mitochondrial localization based on homologous annotation (HDA). PMID:24769239 is a quantitative proteomics study of the mitochondrial proteome that identified CAT2. This provides evidence for mitochondrial localization through detection of the protein in mitochondrial preparations. The annotation is accurate and represents core localization information. Supporting Evidence: PMID:24769239 2014 Apr 24. Quantitative variations of the mitochondrial proteome and phosphoproteome during fermentative and respiratory growth in Saccharomyces cerevisiae.
GO:0005739 mitochondrion	HDA PMID:14576278 The proteome of Saccharomyces cerevisiae mitochondria.	ACCEPT	Summary: This annotation documents mitochondrial localization based on homologous annotation (HDA). PMID:14576278 is a proteomics study of the Saccharomyces cerevisiae mitochondrial proteome, providing evidence for CAT2 identification in mitochondrial preparations. This corroborates the mitochondrial localization annotation. Supporting Evidence: PMID:14576278 The proteome of Saccharomyces cerevisiae mitochondria.
GO:0005739 mitochondrion	HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen...	ACCEPT	Summary: This annotation documents mitochondrial localization based on homologous annotation (HDA). PMID:16823961 is a multidimensional proteomics study toward the complete yeast mitochondrial proteome, providing another line of proteomic evidence for CAT2 identification in mitochondrial preparations. This further corroborates the mitochondrial localization. Supporting Evidence: PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimensional separation techniques for mitochondrial proteomics.
GO:0004092 carnitine O-acetyltransferase activity	IMP PMID:8420957 Cloning and sequencing of a cDNA encoding Saccharomyces cere...	ACCEPT	Summary: This annotation documents carnitine O-acetyltransferase activity based on direct experimental evidence (IMP - Inferred from Mutant Phenotype). PMID:8420957 is the original cloning paper that established CAT2 identity through gene disruption studies and enzyme activity measurements. This is the highest-quality evidence for the enzymatic function. The disruption phenotype (decreased acetylcarnitine content and altered pyruvate metabolism) directly demonstrates the catalytic activity of CAT2. Supporting Evidence: PMID:8420957 A search in the PIR protein data base revealed that besides the known carnitine acyltransferases, choline acyltransferases are highly homologous to yeast CAT file:yeast/CAT2/CAT2-deep-research-falcon.md Cat2p catalyzes the intraperoxisomal conversion of acetyl-CoA into acetylcarnitine (acetyl transfer to carnitine), enabling acetyl-unit transfer out of peroxisomes
GO:0005739 mitochondrion	IDA PMID:18427809 Carnitine and carnitine acetyltransferases in the yeast Sacc...	ACCEPT	Summary: This annotation documents mitochondrial localization based on direct experimental evidence (IDA). PMID:18427809 is a functional study of carnitine acetyltransferases in yeast that documents CAT2 localization and function in stress protection. The direct identification provides evidence for the mitochondrial localization of the primary isoform. This is high-quality evidence for the subcellular localization. Supporting Evidence: PMID:18427809 Carnitine and carnitine acetyltransferases in the yeast Saccharomyces cerevisiae: a role for carnitine in stress protection file:yeast/CAT2/CAT2-deep-research-falcon.md dually localized to peroxisomes and mitochondria
GO:0005777 peroxisome	IDA PMID:18427809 Carnitine and carnitine acetyltransferases in the yeast Sacc...	ACCEPT	Summary: This annotation documents peroxisomal localization based on direct experimental evidence (IDA). PMID:18427809 provides experimental evidence for the peroxisomal isoform of CAT2. The study demonstrates that CAT2 localizes to both mitochondria and peroxisomes, consistent with the documented alternative initiation products that generate two isoforms with different localizations. Supporting Evidence: PMID:18427809 Carnitine and carnitine acetyltransferases in the yeast Saccharomyces cerevisiae: a role for carnitine in stress protection file:yeast/CAT2/CAT2-deep-research-falcon.md two ATG codons can produce isoforms, one containing an N-terminal mitochondrial targeting signal, while a C-terminal PTS1 (AKL)** provides peroxisomal targeting potential
GO:0009437 carnitine metabolic process	IMP PMID:11329169 Carnitine-dependent metabolic activities in Saccharomyces ce...	ACCEPT	Summary: This annotation documents carnitine metabolic process involvement based on direct experimental evidence (IMP - Inferred from Mutant Phenotype). PMID:11329169 is a comprehensive study of carnitine-dependent metabolic activities that demonstrates CAT2 is one of three essential carnitine acetyltransferases. The mutant selection strategy and complementation analysis provide strong genetic evidence for CAT2 involvement in carnitine metabolism. Supporting Evidence: PMID:11329169 L-carnitine is required for the transfer of activated acyl-groups across intracellular membranes in eukaryotic organisms file:yeast/CAT2/CAT2-deep-research-falcon.md peroxisomal CAT forms acetylcarnitine from acetyl-CoA for transport, and mitochondrial CAT catalyzes the reverse reaction to regenerate acetyl-CoA for the TCA cycle