OXCT1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005739 mitochondrion	IBA GO_REF:0000033	ACCEPT	Summary: SCOT is a mitochondrial-matrix enzyme; the phylogenetic (IBA) assignment of mitochondrial localization is well supported and consistent with all other evidence lines for this gene. Reason: SCOT is definitively mitochondrial. UniProt records subcellular location Mitochondrion and a cleaved N-terminal mitochondrial transit peptide (residues 1-39); localization is corroborated by IDA (HPA, PMID:11756565) and HTP (PMID:34800366) evidence. A more specific matrix location is also captured separately (GO:0005759). Supporting Evidence: PMID:8751852 A single approximately
GO:0008260 succinyl-CoA:3-oxo-acid CoA-transferase activity	IBA GO_REF:0000033	ACCEPT	Summary: This is the core catalytic molecular function of SCOT, transferring CoA from succinyl-CoA to a 3-oxo acid (acetoacetate). The IBA assignment matches the experimentally established EC 2.8.3.5 activity. Reason: SCOT (EC 2.8.3.5) catalyzes CoA transfer from succinyl-CoA to acetoacetate, the defining and experimentally validated activity of this protein family. This is the representative core molecular function of the gene. Supporting Evidence: PMID:8751852 mediates the
GO:0005739 mitochondrion	IEA GO_REF:0000044	ACCEPT	Summary: Electronic assignment of mitochondrial localization from the UniProt subcellular-location vocabulary; correct and consistent with the manually curated subcellular location. Reason: UniProt records Mitochondrion as the subcellular location and annotates a mitochondrial transit peptide; this SubCell-derived IEA is accurate. Supporting Evidence: PMID:8751852 A single approximately
GO:0008260 succinyl-CoA:3-oxo-acid CoA-transferase activity	IEA GO_REF:0000120	ACCEPT	Summary: Combined-IEA assignment of the SCOT catalytic activity, mapped from EC 2.8.3.5 and RHEA:24564/25480; matches the experimentally established function. Reason: The mapping is correct - OXCT1 is EC 2.8.3.5 and catalyzes RHEA:24564 (3-oxo acid + succinyl-CoA) and RHEA:25480 (acetoacetate + succinyl-CoA). Duplicate of the IBA/IMP molecular-function annotations, which is acceptable. Supporting Evidence: PMID:10964512 the main determinant of the ketolytic capacity of tissues
GO:0008410 CoA-transferase activity	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: InterPro2GO assignment of the parent term CoA-transferase activity. Correct but less informative than the specific SCOT activity (GO:0008260) that is also annotated. Reason: GO:0008410 is a direct parent of the specific and experimentally supported GO:0008260 succinyl-CoA:3-oxo-acid CoA-transferase activity, which is separately annotated. The parent term is not wrong but is redundant and less informative; the specific child term should be used. Supporting Evidence: PMID:8751852 mediates the
GO:0046952 ketone body catabolic process	IEA GO_REF:0000002	ACCEPT	Summary: SCOT catalyzes the committed, rate-limiting step of ketone-body catabolism (ketolysis). This is the defining biological process for the gene; the InterPro2GO assignment is correct. Reason: SCOT is the key enzyme of ketone-body utilization, activating acetoacetate for downstream oxidation. This is a core biological role, independently supported by experimental (IMP, PMID:9671268) evidence. Supporting Evidence: PMID:9671268 the key enzyme of ketone body utilization
GO:0007507 heart development	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Electronically projected from a rat ortholog (B2GV06). SCOT is most abundantly expressed in myocardium, so a heart-related phenotype is plausible, but this is a tissue-context physiology annotation rather than the gene's core molecular role. Reason: Projected by Ensembl Compara from rat. SCOT is a housekeeping ketolytic enzyme most abundant in heart, so involvement in cardiac physiology is biologically coherent, but heart development is not a core molecular function - it reflects the tissue distribution of a metabolic enzyme. Supporting Evidence: PMID:8751852 heart
GO:0007584 response to nutrient	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Projected from a rat ortholog. Ketolytic flux through SCOT responds to nutritional/fasting state, so this is a plausible physiological context but not the gene's core function. Reason: SCOT-dependent ketone utilization is modulated by nutritional status; the annotation is a coherent physiology context transferred electronically from rat, but is peripheral to the enzyme's core catalytic role. Supporting Evidence: PMID:8751852 for use in energy production
GO:0009410 response to xenobiotic stimulus	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Generic stress-response term electronically projected from a rat expression study. Weakly specific and not clearly related to SCOT function. Reason: This is a nonspecific "response to X" term transferred by Ensembl Compara from a rat ortholog, most likely reflecting expression changes in a treatment experiment. It does not inform SCOT's molecular or metabolic function and is an over-annotation. Supporting Evidence: PMID:10964512 the main determinant of the ketolytic capacity of tissues
GO:0009725 response to hormone	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Projected from a rat ortholog. Ketone-body metabolism is under hormonal control (e.g., insulin/glucagon axis), so this is a plausible physiological context rather than a core function. Reason: Hormonal regulation of ketone metabolism makes this coherent as a physiology context, but the term reflects regulatory responsiveness of a metabolic pathway rather than SCOT's own molecular activity. Supporting Evidence: PMID:10964512 the main determinant of the ketolytic capacity of tissues
GO:0014823 response to activity	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Projected from a rat ortholog, likely reflecting exercise-associated changes in ketolytic tissues (heart, skeletal muscle). Peripheral physiology context. Reason: SCOT is highly expressed in heart and skeletal muscle where ketone utilization supports activity-related energy demand; the electronically transferred term is a coherent physiological context but not a core function. Supporting Evidence: PMID:8751852 for use in energy production
GO:0035774 positive regulation of insulin secretion involved in cellular response to glucose stimulus	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Highly specific regulatory term projected electronically from a rat ortholog. Ketone-body metabolism intersects islet fuel handling, but direct involvement of SCOT in insulin-secretion regulation is not established for human OXCT1. Reason: This specific regulatory phenotype comes from Ensembl Compara transfer from a rat ortholog and reflects a physiological context (islet fuel metabolism) rather than SCOT's molecular function. Retained as non-core pending direct human evidence. Supporting Evidence: PMID:10964512 the main determinant of the ketolytic capacity of tissues
GO:0042594 response to starvation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Projected from a rat ortholog. Ketone bodies are the principal fuel during fasting/starvation, and SCOT enables their utilization, so this is a biologically coherent physiology context. Reason: During starvation, extrahepatic tissues rely on ketolysis, of which SCOT is the rate-limiting enzyme; the term is a coherent physiological context transferred electronically, but is downstream of and secondary to the core catalytic function. Supporting Evidence: PMID:8751852 for use in energy production
GO:0042802 identical protein binding	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: SCOT is a homodimer, so "identical protein binding" is technically true, but this is an uninformative binding term electronically projected from a rat ortholog. Reason: SCOT is a homodimer (UniProt SUBUNIT; PMID:10964512, PMID:23420214), so the term is technically correct, but the biologically meaningful fact (homodimeric enzyme) is captured by the molecular-function annotation and the description. As a generic, electronically projected (IEA) binding term - not experimental IPI - "identical protein binding" adds no functional information and is an over-annotation. Supporting Evidence: PMID:10964512 the main determinant of the ketolytic capacity of tissues
GO:0045471 response to ethanol	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Generic stimulus-response term projected electronically from a rat expression study; not clearly connected to SCOT's characterized function. Reason: A nonspecific "response to ethanol" term transferred by Ensembl Compara from a rat ortholog, most plausibly reflecting expression change in a treatment experiment. It does not inform SCOT's molecular or metabolic role and is an over-annotation. Supporting Evidence: PMID:10964512 the main determinant of the ketolytic capacity of tissues
GO:0060612 adipose tissue development	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Projected from a rat ortholog. SCOT participates in ketone/lipid fuel metabolism in adipose and other tissues, making this a plausible physiology context but not a core function. Reason: SCOT is a broadly expressed ketolytic enzyme; involvement in adipose tissue metabolism/development is a coherent physiological context transferred electronically from rat, but is peripheral to the enzyme's core molecular role. Supporting Evidence: PMID:8751852 for use in energy production
GO:0046952 ketone body catabolic process	IMP PMID:9671268 Succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency: t...	ACCEPT	Summary: Experimental (IMP) support that SCOT is required for ketone-body catabolism - pathogenic SCOT-deficiency mutations abolish enzyme activity and cause episodic ketoacidosis, the metabolic hallmark of impaired ketolysis. Core biological process. Reason: SCOT deficiency (loss-of-function mutations V133E and C456F) produces no detectable SCOT activity and causes episodes of severe ketoacidosis, directly demonstrating SCOT's required role in ketone-body catabolism. This is a core biological process for the gene. Supporting Evidence: PMID:9671268 causes episodes of severe ketoacidosis PMID:9671268 produces no detectable
GO:0005739 mitochondrion	IDA GO_REF:0000052	ACCEPT	Summary: Direct immunofluorescence (HPA) localization of OXCT1 to mitochondrion; consistent with all other evidence. Reason: Direct assay (immunofluorescence, Human Protein Atlas) confirms mitochondrial localization, agreeing with the curated UniProt subcellular location and the matrix-specific Reactome annotations. Supporting Evidence: PMID:8751852 A single approximately
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	ACCEPT	Summary: High-throughput mitochondrial-proteome study identifying OXCT1 as a mitochondrial protein. Consistent with the well-established localization. Reason: A high-confidence quantitative mitochondrial-proteome analysis places OXCT1 in the mitochondrion, corroborating the IDA/IBA/SubCell evidence. Correct compartment. Supporting Evidence: PMID:8751852 A single approximately
GO:0008260 succinyl-CoA:3-oxo-acid CoA-transferase activity	IMP PMID:10964512 Succinyl-CoA:3-ketoacid CoA transferase (SCOT): cloning of t...	ACCEPT	Summary: Experimental (IMP) support for SCOT catalytic activity - pathogenic missense mutations characterized by transient-expression enzyme assays abolish or reduce SCOT activity, establishing the molecular function of the encoded protein. Reason: Fukao et al. cloned the human SCOT gene and characterized pathogenic mutations that abolish enzyme activity (G219E, G324E produced no detectable activity), demonstrating that OXCT1 encodes the succinyl-CoA:3-oxoacid CoA-transferase. Core molecular function with direct experimental support. Supporting Evidence: PMID:10964512 no detectable activity PMID:10964512 the main determinant of the ketolytic capacity of tissues
GO:0008260 succinyl-CoA:3-oxo-acid CoA-transferase activity	IMP PMID:8751852 Succinyl CoA: 3-oxoacid CoA transferase (SCOT): human cDNA c...	ACCEPT	Summary: Experimental (IMP) support - cloning of human SCOT cDNA and detection of a pathogenic nonsense mutation (S283X) incompatible with normal enzyme function, establishing OXCT1 as the SCOT enzyme mediating the rate-determining step of ketolysis. Reason: Kassovska-Bratinova et al. cloned human heart SCOT cDNA and identified a homozygous mutation incompatible with normal enzyme function in a SCOT-deficient patient, establishing the encoded protein's succinyl-CoA:3-oxoacid CoA-transferase activity. Core molecular function. Supporting Evidence: PMID:8751852 rate-determining step of ketolysis in extrahepatic
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-74177	ACCEPT	Summary: Reactome curation of the SCOT reaction (CoA transfer from succinyl-CoA to acetoacetate) places OXCT1 in the mitochondrial matrix. This is the correct, more specific compartment for the soluble matrix enzyme. Reason: SCOT is a soluble matrix enzyme of ketolysis; the Reactome-derived matrix localization is more informative than the general "mitochondrion" term and is correct. Supporting Evidence: PMID:8751852 rate-determining step of ketolysis in extrahepatic
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9838035	ACCEPT	Summary: Matrix localization from a Reactome reaction (CLPXP binding of mitochondrial matrix proteins). Localization is correct; the reaction is a generic matrix-protein-handling event. Reason: The compartment assignment (mitochondrial matrix) is correct and consistent with the primary SCOT reaction annotation, even though this particular Reactome event is a generic matrix protein-quality-control reaction. Supporting Evidence: PMID:8751852 rate-determining step of ketolysis in extrahepatic
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9838081	ACCEPT	Summary: Matrix localization from a Reactome reaction (LONP1 degradation of mitochondrial matrix proteins). Localization is correct. Reason: The mitochondrial-matrix compartment assignment is correct; the underlying Reactome event is a generic matrix protein-degradation reaction but the localization it implies for OXCT1 is accurate. Supporting Evidence: PMID:8751852 rate-determining step of ketolysis in extrahepatic
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9838093	ACCEPT	Summary: Matrix localization from a Reactome reaction (LONP1 binding of mitochondrial matrix proteins). Localization is correct. Reason: The mitochondrial-matrix compartment assignment is correct and consistent with the primary SCOT annotation; the underlying event is a generic matrix protein-binding reaction. Supporting Evidence: PMID:8751852 rate-determining step of ketolysis in extrahepatic
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9838289	ACCEPT	Summary: Matrix localization from a Reactome reaction (CLPXP degradation of mitochondrial matrix proteins). Localization is correct. Reason: The mitochondrial-matrix compartment assignment is correct; the underlying Reactome event is a generic matrix protein-degradation reaction but the implied localization for OXCT1 is accurate. Supporting Evidence: PMID:8751852 rate-determining step of ketolysis in extrahepatic
GO:0005739 mitochondrion	IDA PMID:11756565 Cloning and characterization of a human orthologue of testis...	ACCEPT	Summary: Direct (IDA) localization of a SCOT-family protein to the mitochondria-containing midpiece of spermatozoa. Note this paper characterizes the testis-specific paralog SCOT-t (OXCT2); the annotation supports mitochondrial localization for the SCOT family and is retained as CC support. Reason: This study directly localized the SCOT-t protein to the sperm midpiece where mitochondria are concentrated. Although the paper focuses on the testis-specific paralog, the annotation is to the general and uncontested "mitochondrion" compartment, is experimental (IDA), and is consistent with all other evidence; per curation policy an experimental localization annotation is not removed on the basis of paralog/title considerations. Supporting Evidence: PMID:11756565 the protein was localized to the midpiece of ejaculated spermatozoa PMID:11756565 where mitochondria exist
GO:0005739 mitochondrion	NAS PMID:10964512 Succinyl-CoA:3-ketoacid CoA transferase (SCOT): cloning of t...	ACCEPT	Summary: Non-traceable author statement of mitochondrial localization from the human SCOT gene-cloning paper. Consistent with the well-established localization. Reason: The mitochondrial localization asserted here matches the curated UniProt subcellular location and multiple experimental (IDA/HTP) and Reactome (matrix) annotations. Correct compartment. Supporting Evidence: PMID:10964512 the main determinant of the ketolytic capacity of tissues

Gene Description

Existing Annotations Review

Core Functions

Succinyl-CoA:3-oxoacid CoA-transferase (SCOT) activity - transfers CoA from succinyl-CoA to acetoacetate to form acetoacetyl-CoA and succinate, catalyzing the committed, rate-limiting step of ketone-body utilization (ketolysis) in the mitochondrial matrix of extrahepatic tissues.

References

📚 Additional Documentation

Notes

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