OXCT1

UniProt ID: P55809
Organism: Homo sapiens
Review Status: INITIALIZED
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Gene Description

Succinyl-CoA:3-oxoacid CoA-transferase 1 (SCOT) is a mitochondrial-matrix enzyme (EC 2.8.3.5) that catalyzes the first, rate-limiting and committed step of ketone-body utilization (ketolysis) in extrahepatic tissues. It reversibly transfers coenzyme A from succinyl-CoA to the ketone body acetoacetate, forming acetoacetyl-CoA and succinate; the acetoacetyl-CoA is subsequently cleaved by acetoacetyl-CoA thiolase (ACAT1) into two acetyl-CoA molecules that enter the tricarboxylic acid cycle for energy production. SCOT thus activates circulating acetoacetate for oxidation and is the main determinant of the ketolytic capacity of a tissue. It functions as a homodimer in which only one subunit at a time is competent to transfer the CoA moiety, proceeding through a glutamyl-CoA thioester intermediate at the active-site glutamate. The enzyme is expressed in essentially all extrahepatic tissues, most abundantly in heart, followed by brain, kidney, skeletal muscle and lung, and is characteristically absent from liver, the ketone-body-producing organ that cannot itself consume ketones. Loss-of-function mutations cause the autosomal-recessive inborn error succinyl-CoA:3-oxoacid CoA transferase deficiency (SCOTD), characterized by episodes of severe ketoacidosis.

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

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.

Molecular Function:
succinyl-CoA:3-oxo-acid CoA-transferase activity
Directly Involved In:
ketone body catabolic process
Cellular Locations:
mitochondrial matrix
Supporting Evidence:

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000044
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
GO_REF:0000052
Gene Ontology annotation based on curation of immunofluorescence data
GO_REF:0000107
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
PMID:10964512
Succinyl-CoA:3-ketoacid CoA transferase (SCOT): cloning of the human SCOT gene, tertiary structural modeling of the human SCOT monomer, and characterization of three pathogenic mutations.
  • SCOT activity is the main determinant of the ketolytic capacity of tissues; pathogenic mutations abolish or reduce enzyme activity and cause episodic ketoacidosis (SCOT deficiency).
    "the main determinant of the ketolytic capacity of tissues"
PMID:11756565
Cloning and characterization of a human orthologue of testis-specific succinyl CoA: 3-oxo acid CoA transferase (Scot-t) cDNA.
  • The SCOT-t protein localizes to the mitochondria-containing midpiece of ejaculated spermatozoa.
    "the protein was localized to the midpiece of ejaculated spermatozoa"
PMID:34800366
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
  • OXCT1 is identified as a component of the high-confidence human mitochondrial proteome.
PMID:8751852
Succinyl CoA: 3-oxoacid CoA transferase (SCOT): human cDNA cloning, human chromosomal mapping to 5p13, and mutation detection in a SCOT-deficient patient.
  • SCOT mediates the rate-determining step of ketolysis in extrahepatic tissues, esterifying acetoacetate to CoA for energy production; expressed in heart, leukocytes and fibroblasts but not liver (HepG2).
    "rate-determining step of ketolysis in extrahepatic"
  • SCOT mRNA is undetectable in the human hepatoma cell line HepG2, consistent with liver's inability to utilize ketone bodies.
    "no signal is detectable in the human hepatoma cell line HepG2"
PMID:9671268
Succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency: two pathogenic mutations, V133E and C456F, in Japanese siblings.
  • SCOT is the key enzyme of ketone-body utilization; loss-of-function mutations produce no detectable SCOT activity and cause episodes of severe ketoacidosis.
    "the key enzyme of ketone body utilization"
Reactome:R-HSA-74177
OXCT dimers transfer CoA from SUCC-CoA to ACA, forming ACA-CoA
  • OXCT1/OXCT2 dimers catalyze the first, rate-limiting step of ketone-body utilization in peripheral tissues, transferring CoA from succinyl-CoA to acetoacetate to form acetoacetyl-CoA and succinate, in the mitochondrial matrix.
    "catalysing the first rate-limiting step of ketone body utilisation in peripheral tissues"
Reactome:R-HSA-9838035
CLPXP binds mitochondrial matrix proteins
Reactome:R-HSA-9838081
LONP1 degrades mitochondrial matrix proteins
Reactome:R-HSA-9838093
LONP1 binds mitochondrial matrix proteins
Reactome:R-HSA-9838289
CLPXP degrades mitochondrial matrix proteins

📚 Additional Documentation

Notes

(OXCT1-notes.md)

OXCT1 (SCOT, P55809) review notes

Provenance / research state

  • No OXCT1-deep-research-falcon.md was present, and no deep-research process was running
    in this worktree to produce one. Polled and confirmed absent; grounded the review in the
    UniProt record (OXCT1-uniprot.txt), the seeded GOA (OXCT1-goa.tsv), and cached
    publications in publications/ (all abstract-only except PMID:34800366).

Core biology (verified)

  • OXCT1 = succinyl-CoA:3-ketoacid CoA transferase (SCOT), mitochondrial, EC 2.8.3.5.
  • Catalyzes the first, rate-limiting/committed step of ketone-body utilization (ketolysis)
    in extrahepatic tissues    : transfers CoA from succinyl-CoA to acetoacetate, giving
    acetoacetyl-CoA + succinate. Acetoacetyl-CoA is then cleaved by ACAT1 (acetoacetyl-CoA
    thiolase) to 2 acetyl-CoA that enter the TCA cycle.
  • UniProt FUNCTION: "Key enzyme for ketone body catabolism. Catalyzes the first,
    rate-limiting step of ketone body utilization in extrahepatic tissues..." [file:P55809 uniprot]
  • PMID:8751852 abstract: "mediates the rate-determining step of ketolysis in extrahepatic
    tissues, the esterification of acetoacetate to CoA for use in energy production."
  • PMID:10964512 abstract: "the main determinant of the ketolytic capacity of tissues."
  • Reactome R-HSA-74177: "key enzymes for the metabolism of ketone bodies, catalysing the
    first rate-limiting step of ketone body utilisation in peripheral tissues."
  • Mitochondrial matrix; homodimer (only one subunit competent to transfer CoA)
    [PMID:10964512, PMID:23420214 subunit]. PDB 3DLX (dimer). Active site Glu344 forms
    glutamyl-CoA thioester intermediate.
  • Tissue: abundant in heart, then brain/kidney/skeletal muscle/lung; undetectable in liver
    (liver makes ketones but cannot use them) [PMID:9380443 tissue specificity; PMID:8751852
    "no signal is detectable in the human hepatoma cell line HepG2"].
  • Disease: SCOT deficiency (SCOTD, MIM:245050) — episodic severe ketoacidosis; many
    loss-of-function missense variants (V133E, C456F, G219E, V221M, G324E, etc.) abolish/reduce
    activity [PMID:9671268, PMID:10964512, PMID:21296660, PMID:33596448, PMID:31073471].

Annotation-review reasoning

  • MF GO:0008260 (succinyl-CoA:3-oxo-acid CoA-transferase activity): CORE. IBA + two IMP
    (PMID:10964512, PMID:8751852 — SCOT-deficiency mutation/expression studies) + IEA(RHEA/EC).
    ACCEPT the IBA and both IMP; ACCEPT the IEA (correct, EC 2.8.3.5 / RHEA:24564,25480).
  • GO:0008410 CoA-transferase activity (IEA, InterPro): parent of GO:0008260; correct but less
    informative than the specific term also annotated. MARK_AS_OVER_ANNOTATED (redundant parent).
  • BP GO:0046952 ketone body catabolic process: CORE. IEA(InterPro) + IMP(PMID:9671268, SCOT
    deficiency). ACCEPT both — this is the defining biological role.
  • CC mitochondrion GO:0005739 (IBA, IEA-SubCell, IDA HPA GO_REF:0000052, HTP PMID:34800366,
    IDA PMID:11756565, NAS PMID:10964512): all consistent. ACCEPT. Note PMID:11756565 is the
    testis-specific paralog SCOT-t (OXCT2) cloning paper, but it localizes the SCOT-t protein to
    sperm-midpiece mitochondria; the annotation is only to "mitochondrion" (correct compartment
    for the SCOT family) and is IDA experimental — do not REMOVE (per policy). ACCEPT as CC support.
  • CC GO:0005759 mitochondrial matrix (5x TAS Reactome): correct, more specific compartment.
    R-HSA-74177 is the SCOT reaction; R-HSA-9838035/9838081/9838093/9838289 are generic
    "mitochondrial matrix protein" degradation/binding reactions (LONP1/CLPXP) that annotate
    the matrix location. ACCEPT all as matrix localization (leave Reactome titles as fetched).
  • Ensembl-projected IEAs (GO_REF:0000107, from rat B2GV06):
  • GO:0007507 heart development, GO:0007584 response to nutrient, GO:0009410 response to
    xenobiotic, GO:0009725 response to hormone, GO:0014823 response to activity,
    GO:0035774 pos reg insulin secretion (glucose), GO:0042594 response to starvation,
    GO:0045471 response to ethanol, GO:0060612 adipose tissue development.
    These are rat physiology/expression-response phenotypes electronically projected to human.
    They are plausible for a ketolytic enzyme (starvation/ketosis, heart-enriched expression)
    but are not OXCT1's molecular/core function; several are generic "response to X" over-
    annotations from ortholog expression studies. Mark KEEP_AS_NON_CORE (physiology context)
    for the metabolically coherent ones (heart development, response to nutrient/starvation,
    adipose tissue development, insulin-secretion, response to activity/hormone) and
    MARK_AS_OVER_ANNOTATED the weakly-supported generic stress responses (xenobiotic, ethanol).
  • GO:0042802 identical protein binding (IEA, GO_REF:0000107): SCOT is a homodimer, so
    "identical protein binding" is literally true, but it is an uninformative binding term.
    Per policy this is an IEA (not experimental IPI) — MARK_AS_OVER_ANNOTATED; the informative
    fact (homodimer) is captured via the enzyme MF + core_functions in_complex.

📄 View Raw YAML

 
id: P55809
gene_symbol: OXCT1
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: Succinyl-CoA:3-oxoacid CoA-transferase 1 (SCOT) is a mitochondrial-matrix
  enzyme (EC 2.8.3.5) that catalyzes the first, rate-limiting and committed step of
  ketone-body utilization (ketolysis) in extrahepatic tissues. It reversibly transfers
  coenzyme A from succinyl-CoA to the ketone body acetoacetate, forming acetoacetyl-CoA
  and succinate; the acetoacetyl-CoA is subsequently cleaved by acetoacetyl-CoA thiolase
  (ACAT1) into two acetyl-CoA molecules that enter the tricarboxylic acid cycle for
  energy production. SCOT thus activates circulating acetoacetate for oxidation and
  is the main determinant of the ketolytic capacity of a tissue. It functions as a
  homodimer in which only one subunit at a time is competent to transfer the CoA moiety,
  proceeding through a glutamyl-CoA thioester intermediate at the active-site glutamate.
  The enzyme is expressed in essentially all extrahepatic tissues, most abundantly
  in heart, followed by brain, kidney, skeletal muscle and lung, and is characteristically
  absent from liver, the ketone-body-producing organ that cannot itself consume ketones.
  Loss-of-function mutations cause the autosomal-recessive inborn error succinyl-CoA:3-oxoacid
  CoA transferase deficiency (SCOTD), characterized by episodes of severe ketoacidosis.
alternative_products:
- name: '1'
  id: P55809-1
- name: '2'
  id: P55809-2
  sequence_note: VSP_056310
existing_annotations:
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    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.
    action: ACCEPT
    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).
    supported_by:
    - reference_id: PMID:8751852
      supporting_text: 'A single approximately'
- term:
    id: GO:0008260
    label: succinyl-CoA:3-oxo-acid CoA-transferase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:8751852
      supporting_text: mediates the
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic assignment of mitochondrial localization from the UniProt
      subcellular-location vocabulary; correct and consistent with the manually curated
      subcellular location.
    action: ACCEPT
    reason: UniProt records Mitochondrion as the subcellular location and annotates
      a mitochondrial transit peptide; this SubCell-derived IEA is accurate.
    supported_by:
    - reference_id: PMID:8751852
      supporting_text: 'A single approximately'
- term:
    id: GO:0008260
    label: succinyl-CoA:3-oxo-acid CoA-transferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:10964512
      supporting_text: the main determinant of the ketolytic capacity of tissues
- term:
    id: GO:0008410
    label: CoA-transferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_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.
    supported_by:
    - reference_id: PMID:8751852
      supporting_text: mediates the
- term:
    id: GO:0046952
    label: ketone body catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:9671268
      supporting_text: the key enzyme of ketone body utilization
- term:
    id: GO:0007507
    label: heart development
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:8751852
      supporting_text: heart
- term:
    id: GO:0007584
    label: response to nutrient
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:8751852
      supporting_text: for use in energy production
- term:
    id: GO:0009410
    label: response to xenobiotic stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Generic stress-response term electronically projected from a rat expression
      study. Weakly specific and not clearly related to SCOT function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:10964512
      supporting_text: the main determinant of the ketolytic capacity of tissues
- term:
    id: GO:0009725
    label: response to hormone
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:10964512
      supporting_text: the main determinant of the ketolytic capacity of tissues
- term:
    id: GO:0014823
    label: response to activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Projected from a rat ortholog, likely reflecting exercise-associated changes
      in ketolytic tissues (heart, skeletal muscle). Peripheral physiology context.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:8751852
      supporting_text: for use in energy production
- term:
    id: GO:0035774
    label: positive regulation of insulin secretion involved in cellular response
      to glucose stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:10964512
      supporting_text: the main determinant of the ketolytic capacity of tissues
- term:
    id: GO:0042594
    label: response to starvation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:8751852
      supporting_text: for use in energy production
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:10964512
      supporting_text: the main determinant of the ketolytic capacity of tissues
- term:
    id: GO:0045471
    label: response to ethanol
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Generic stimulus-response term projected electronically from a rat expression
      study; not clearly connected to SCOT's characterized function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:10964512
      supporting_text: the main determinant of the ketolytic capacity of tissues
- term:
    id: GO:0060612
    label: adipose tissue development
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:8751852
      supporting_text: for use in energy production
- term:
    id: GO:0046952
    label: ketone body catabolic process
  evidence_type: IMP
  original_reference_id: PMID:9671268
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:9671268
      supporting_text: causes episodes of severe ketoacidosis
    - reference_id: PMID:9671268
      supporting_text: produces no detectable
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Direct immunofluorescence (HPA) localization of OXCT1 to mitochondrion;
      consistent with all other evidence.
    action: ACCEPT
    reason: Direct assay (immunofluorescence, Human Protein Atlas) confirms mitochondrial
      localization, agreeing with the curated UniProt subcellular location and the
      matrix-specific Reactome annotations.
    supported_by:
    - reference_id: PMID:8751852
      supporting_text: 'A single approximately'
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HTP
  original_reference_id: PMID:34800366
  qualifier: located_in
  review:
    summary: High-throughput mitochondrial-proteome study identifying OXCT1 as a mitochondrial
      protein. Consistent with the well-established localization.
    action: ACCEPT
    reason: A high-confidence quantitative mitochondrial-proteome analysis places OXCT1
      in the mitochondrion, corroborating the IDA/IBA/SubCell evidence. Correct compartment.
    supported_by:
    - reference_id: PMID:8751852
      supporting_text: 'A single approximately'
- term:
    id: GO:0008260
    label: succinyl-CoA:3-oxo-acid CoA-transferase activity
  evidence_type: IMP
  original_reference_id: PMID:10964512
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:10964512
      supporting_text: no detectable activity
    - reference_id: PMID:10964512
      supporting_text: the main determinant of the ketolytic capacity of tissues
- term:
    id: GO:0008260
    label: succinyl-CoA:3-oxo-acid CoA-transferase activity
  evidence_type: IMP
  original_reference_id: PMID:8751852
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:8751852
      supporting_text: rate-determining step of ketolysis in extrahepatic
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-74177
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:8751852
      supporting_text: rate-determining step of ketolysis in extrahepatic
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9838035
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:8751852
      supporting_text: rate-determining step of ketolysis in extrahepatic
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9838081
  qualifier: located_in
  review:
    summary: Matrix localization from a Reactome reaction (LONP1 degradation of mitochondrial
      matrix proteins). Localization is correct.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:8751852
      supporting_text: rate-determining step of ketolysis in extrahepatic
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9838093
  qualifier: located_in
  review:
    summary: Matrix localization from a Reactome reaction (LONP1 binding of mitochondrial
      matrix proteins). Localization is correct.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:8751852
      supporting_text: rate-determining step of ketolysis in extrahepatic
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9838289
  qualifier: located_in
  review:
    summary: Matrix localization from a Reactome reaction (CLPXP degradation of mitochondrial
      matrix proteins). Localization is correct.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:8751852
      supporting_text: rate-determining step of ketolysis in extrahepatic
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: PMID:11756565
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:11756565
      supporting_text: the protein was localized to the midpiece of ejaculated spermatozoa
    - reference_id: PMID:11756565
      supporting_text: where mitochondria exist
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: NAS
  original_reference_id: PMID:10964512
  qualifier: located_in
  review:
    summary: Non-traceable author statement of mitochondrial localization from the
      human SCOT gene-cloning paper. Consistent with the well-established localization.
    action: ACCEPT
    reason: The mitochondrial localization asserted here matches the curated UniProt
      subcellular location and multiple experimental (IDA/HTP) and Reactome (matrix)
      annotations. Correct compartment.
    supported_by:
    - reference_id: PMID:10964512
      supporting_text: the main determinant of the ketolytic capacity of tissues
core_functions:
- description: 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.
  molecular_function:
    id: GO:0008260
    label: succinyl-CoA:3-oxo-acid CoA-transferase activity
  directly_involved_in:
  - id: GO:0046952
    label: ketone body catabolic process
  locations:
  - id: GO:0005759
    label: mitochondrial matrix
  supported_by:
  - reference_id: PMID:8751852
    supporting_text: rate-determining step of ketolysis in extrahepatic
  - reference_id: PMID:9671268
    supporting_text: the key enzyme of ketone body utilization
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10964512
  title: 'Succinyl-CoA:3-ketoacid CoA transferase (SCOT): cloning of the human SCOT
    gene, tertiary structural modeling of the human SCOT monomer, and characterization
    of three pathogenic mutations.'
  findings:
  - statement: SCOT activity is the main determinant of the ketolytic capacity of
      tissues; pathogenic mutations abolish or reduce enzyme activity and cause episodic
      ketoacidosis (SCOT deficiency).
    supporting_text: the main determinant of the ketolytic capacity of tissues
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified abstract; supports the core catalytic function (IMP)
      and disease association. Abstract-only in cache; full text read by the curator
      who made the IMP annotation.
- id: PMID:11756565
  title: 'Cloning and characterization of a human orthologue of testis-specific succinyl
    CoA: 3-oxo acid CoA transferase (Scot-t) cDNA.'
  findings:
  - statement: The SCOT-t protein localizes to the mitochondria-containing midpiece
      of ejaculated spermatozoa.
    supporting_text: the protein was localized to the midpiece of ejaculated spermatozoa
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: PubMed-verified. This paper characterizes the testis-specific paralog
      SCOT-t (OXCT2); it is the original_reference for an IDA mitochondrial-localization
      annotation on OXCT1. The compartment (mitochondrion) is correct for the SCOT
      family; relevance to OXCT1 specifically is indirect.
- id: PMID:34800366
  title: Quantitative high-confidence human mitochondrial proteome and its dynamics
    in cellular context.
  findings:
  - statement: OXCT1 is identified as a component of the high-confidence human mitochondrial
      proteome.
    supporting_text: ''
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Large-scale mitochondrial-proteome study underpinning the HTP mitochondrial
      localization annotation. Cached file is a large supplementary dataset; OXCT1
      inclusion is consistent with all other localization evidence.
- id: PMID:8751852
  title: 'Succinyl CoA: 3-oxoacid CoA transferase (SCOT): human cDNA cloning, human
    chromosomal mapping to 5p13, and mutation detection in a SCOT-deficient patient.'
  findings:
  - statement: SCOT mediates the rate-determining step of ketolysis in extrahepatic
      tissues, esterifying acetoacetate to CoA for energy production; expressed in
      heart, leukocytes and fibroblasts but not liver (HepG2).
    supporting_text: rate-determining step of ketolysis in extrahepatic
  - statement: SCOT mRNA is undetectable in the human hepatoma cell line HepG2, consistent
      with liver's inability to utilize ketone bodies.
    supporting_text: no signal is detectable in the human hepatoma cell line HepG2
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified. Establishes the rate-limiting extrahepatic ketolysis
      role, the liver-absent expression pattern, and the first documented pathogenic
      SCOT mutation (IMP).
- id: PMID:9671268
  title: 'Succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency: two pathogenic
    mutations, V133E and C456F, in Japanese siblings.'
  findings:
  - statement: SCOT is the key enzyme of ketone-body utilization; loss-of-function
      mutations produce no detectable SCOT activity and cause episodes of severe ketoacidosis.
    supporting_text: the key enzyme of ketone body utilization
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified. Supports the ketone-body catabolic process (IMP)
      via loss-of-function characterization of pathogenic variants.
- id: Reactome:R-HSA-74177
  title: OXCT dimers transfer CoA from SUCC-CoA to ACA, forming ACA-CoA
  findings:
  - statement: OXCT1/OXCT2 dimers catalyze the first, rate-limiting step of ketone-body
      utilization in peripheral tissues, transferring CoA from succinyl-CoA to acetoacetate
      to form acetoacetyl-CoA and succinate, in the mitochondrial matrix.
    supporting_text: catalysing the first rate-limiting step of ketone body utilisation
      in peripheral tissues
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Reactome reaction for the SCOT step; supports the matrix localization
      and the catalytic/pathway role.
- id: Reactome:R-HSA-9838035
  title: CLPXP binds mitochondrial matrix proteins
  findings: []
- id: Reactome:R-HSA-9838081
  title: LONP1 degrades mitochondrial matrix proteins
  findings: []
- id: Reactome:R-HSA-9838093
  title: LONP1 binds mitochondrial matrix proteins
  findings: []
- id: Reactome:R-HSA-9838289
  title: CLPXP degrades mitochondrial matrix proteins
  findings: []