CPT1A

UniProt ID: P50416
Organism: Homo sapiens
Review Status: INITIALIZED
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Gene Description

Carnitine O-palmitoyltransferase 1, liver isoform (CPT1A) is the liver-type isoform of carnitine palmitoyltransferase 1, a multi-pass protein of the mitochondrial outer membrane with a large cytoplasmic C-terminal catalytic domain. It catalyzes the committed, rate-limiting step of long-chain fatty acid entry into mitochondria for beta-oxidation, transferring the acyl group of long-chain acyl-CoA thioesters (e.g. palmitoyl-CoA) onto L-carnitine to form long-chain acylcarnitine plus CoA (EC 2.3.1.21). As the principal regulatory node of the carnitine shuttle, its activity is allosterically inhibited by malonyl-CoA, coupling fatty-acid oxidation to fatty-acid synthesis and nutritional state. Loss-of-function variants cause carnitine palmitoyltransferase 1A deficiency, an autosomal recessive disorder of fatty-acid oxidation presenting with hypoketotic hypoglycemia. Beyond its canonical acyltransferase role, CPT1A has reported secondary activities, including a lysine succinyltransferase activity and a catalysis-independent scaffolding function that recruits ZDHHC4 to promote MAVS palmitoylation and sustain the type I interferon response.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0004095 carnitine O-palmitoyltransferase activity
IBA
GO_REF:0000033 		ACCEPT
Summary: Phylogenetic (IBA) assignment of the defining molecular function of CPT1A, transfer of a long-chain acyl group from acyl-CoA to carnitine. This is strongly supported by direct experimental characterization of the human enzyme and is the core function of the gene.
Reason: The carnitine O-palmitoyltransferase activity (EC 2.3.1.21) is the well-established catalytic function of CPT1A and is the correct level of specificity. It is corroborated by multiple experimental annotations in this dataset.
Supporting Evidence:
PMID:14517221
Carnitine palmitoyltransferase 1A (CPT1A) is the
GO:0005739 mitochondrion
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: Phylogenetic assignment placing CPT1A activity in the mitochondrion. Correct but less specific than the experimentally supported mitochondrial outer membrane localization.
Reason: The mitochondrion is a true but general compartment; the specific and informative localization is the mitochondrial outer membrane (GO:0005741), which is captured by experimental annotations. Retained as non-core parent term.
Supporting Evidence:
PMID:11350182
alters neither mitochondrial targeting nor stability of the CPT1A
GO:0006631 fatty acid metabolic process
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: Phylogenetic assignment of a general fatty acid metabolic role. True but a broad parent of the more specific beta-oxidation / long-chain fatty acid metabolic terms.
Reason: CPT1A is genuinely involved in fatty acid metabolism, but this term is a general parent; the specific process is long-chain fatty acid import for beta-oxidation (GO:0006635, GO:0001676). Kept as non-core.
Supporting Evidence:
PMID:14517221
key regulatory enzyme of
GO:0009437 carnitine metabolic process
IBA
GO_REF:0000033 		ACCEPT
Summary: Phylogenetic assignment of a carnitine metabolic role, consistent with CPT1A producing acylcarnitine from carnitine as part of the carnitine shuttle.
Reason: CPT1A consumes L-carnitine to generate long-chain acylcarnitine, directly participating in carnitine metabolism; supported experimentally (PMID:11350182, IDA in this dataset).
Supporting Evidence:
PMID:14517221
Carnitine palmitoyltransferase 1A (CPT1A) is the
GO:0004095 carnitine O-palmitoyltransferase activity
IEA
GO_REF:0000120 		ACCEPT
Summary: Electronic assignment (ARBA/RHEA/EC 2.3.1.21) of the core carnitine O-palmitoyltransferase activity, matching the experimentally established function.
Reason: Correct and specific molecular function, consistent with the RHEA:12661 reaction and EC 2.3.1.21 in the UniProt record and multiple experimental annotations.
Supporting Evidence:
PMID:14517221
Carnitine palmitoyltransferase 1A (CPT1A) is the
GO:0005741 mitochondrial outer membrane
IEA
GO_REF:0000120 		ACCEPT
Summary: Electronic assignment of the mitochondrial outer membrane localization, matching the experimentally verified subcellular location of CPT1A.
Reason: The mitochondrial outer membrane is the correct, specific compartment for CPT1A and is supported experimentally (PMID:11350182, PMID:14517221) and by the UniProt SUBCELLULAR LOCATION statement.
Supporting Evidence:
PMID:16651524
an outer mitochondrial membrane enzyme
GO:0006853 carnitine shuttle
IEA
GO_REF:0000117 		ACCEPT
Summary: Electronic (ARBA) assignment of the carnitine shuttle process. CPT1A catalyzes the first, committed step of the carnitine shuttle that imports long-chain fatty acids into mitochondria.
Reason: CPT1A performs the rate-limiting acylcarnitine-forming step of the carnitine shuttle; a correct and specific process term. Corroborated by the Reactome TAS annotation to the same term.
Supporting Evidence:
PMID:16651524
controls entry of fatty acids into mitochondria and, thereby, fatty acid oxidation
GO:0016746 acyltransferase activity
IEA
GO_REF:0000002 		MARK AS OVER ANNOTATED
Summary: InterPro-based electronic assignment of the general acyltransferase activity (from the carnitine acyltransferase domain IPR000542). This is a broad parent of the specific carnitine O-palmitoyltransferase activity.
Reason: Not wrong, but a general parent of GO:0004095 which is annotated more precisely. The specific carnitine O-palmitoyltransferase activity should be preferred as the informative molecular function.
GO:0001666 response to hypoxia
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Electronic transfer of a rat-ortholog phenotype/expression annotation. Reflects downstream physiology rather than CPT1A's molecular function.
Reason: Response to hypoxia is a plausible physiological context for fatty-acid oxidation regulation but is transferred from the rat ortholog and is not a core molecular activity of CPT1A. Retained as non-core.
GO:0001676 long-chain fatty acid metabolic process
IEA
GO_REF:0000107 		ACCEPT
Summary: Electronic assignment of long-chain fatty acid metabolic process, matching the substrate specificity of CPT1A (long-chain acyl-CoA thioesters).
Reason: CPT1A acts specifically on long-chain acyl-CoA substrates to enable their mitochondrial oxidation; this specific process term is well supported (also IDA PMID:11350182 in this dataset).
Supporting Evidence:
PMID:14517221
hepatic long-chain fatty acid beta-oxidation
GO:0006006 glucose metabolic process
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Electronic transfer from the rat ortholog. Reflects the indirect metabolic influence of fatty-acid oxidation on glucose handling rather than a direct role.
Reason: Any effect on glucose metabolism is downstream/indirect (fatty-acid oxidation spares glucose); not a core CPT1A function. Retained as non-core.
GO:0006631 fatty acid metabolic process
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Electronic assignment of the general fatty acid metabolic process, duplicating the IBA annotation to the same broad parent term.
Reason: True but general; the specific process is long-chain fatty acid import for beta-oxidation. Kept as non-core parent.
GO:0006635 fatty acid beta-oxidation
IEA
GO_REF:0000120 		ACCEPT
Summary: Electronic assignment (ARBA/UniPathway UPA00659) of fatty acid beta-oxidation. CPT1A catalyzes the rate-limiting import step required for mitochondrial beta-oxidation of long-chain fatty acids.
Reason: CPT1A is the committed step controlling long-chain fatty-acid entry for beta-oxidation; a correct and central process term, corroborated by TAS (PMID:7892212) and ISS annotations.
Supporting Evidence:
PMID:9691089
decreased rate of fatty acid beta-oxidation
GO:0006641 triglyceride metabolic process
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Electronic transfer from the rat ortholog. UniProt notes a role in hepatic triglyceride metabolism (by similarity), but this is a downstream/indirect physiological consequence.
Reason: Consistent with a hepatic triglyceride-metabolism role inferred by similarity, but indirect relative to the core acyltransferase function. Retained as non-core.
GO:0007584 response to nutrient
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Electronic transfer from the rat ortholog capturing nutritional regulation of CPT1A/fatty-acid oxidation.
Reason: Reflects physiological regulation (CPT1A is induced by fatty acids and regulated by nutritional state) rather than a core molecular function. Retained as non-core.
GO:0009410 response to xenobiotic stimulus
IEA
GO_REF:0000107 		MARK AS OVER ANNOTATED
Summary: Electronic transfer from the rat ortholog. Off-context response term with no direct mechanistic link to CPT1A's function established for human.
Reason: Xenobiotic-response annotation transferred from the rat ortholog does not inform CPT1A's molecular function and is a likely over-annotation for the human gene.
GO:0009437 carnitine metabolic process
IEA
GO_REF:0000107 		ACCEPT
Summary: Electronic assignment of carnitine metabolic process, duplicating the IBA/IDA annotations. Consistent with CPT1A consuming carnitine to form acylcarnitine.
Reason: CPT1A directly participates in carnitine metabolism as part of the carnitine shuttle; correct process term corroborated by experimental (IDA) evidence.
Supporting Evidence:
PMID:16651524
catalyze acyl transfer from various fatty
GO:0031667 response to nutrient levels
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Electronic transfer from the rat ortholog capturing regulation by nutritional state (fasting/feeding).
Reason: Reflects physiological regulation of CPT1A rather than its core molecular activity. Retained as non-core.
GO:0032000 positive regulation of fatty acid beta-oxidation
IEA
GO_REF:0000107 		MARK AS OVER ANNOTATED
Summary: Electronic transfer from the rat ortholog. CPT1A is the enzyme that carries out the rate-limiting step of beta-oxidation; framing this as CPT1A positively regulating beta-oxidation is largely self-referential.
Reason: CPT1A executes the committed step of long-chain beta-oxidation (captured by GO:0006635); a separate positive-regulation term for the enzyme regulating the very process it catalyzes is an over-annotation.
GO:0042755 eating behavior
IEA
GO_REF:0000107 		MARK AS OVER ANNOTATED
Summary: Electronic transfer from the rat ortholog. Eating-behavior/energy-homeostasis roles are best established for the brain isoform CPT1C, not the liver CPT1A.
Reason: Feeding-behavior control via malonyl-CoA sensing is chiefly attributed to the brain-specific CPT1C (PMID:16651524); assigning eating behavior to liver CPT1A by ortholog transfer is a likely over-annotation.
Supporting Evidence:
PMID:16651524
CPT1c KO mice have lower body weight and food intake
GO:0042802 identical protein binding
IEA
GO_REF:0000107 		MARK AS OVER ANNOTATED
Summary: Electronic transfer from the rat ortholog of self-association. CPT1A is reported to form homo-oligomers (homohexamer/homotrimer, by similarity), but the bare identical protein binding term is uninformative about function.
Reason: Although CPT1A oligomerizes, identical protein binding is an uninformative binding term that does not describe a molecular function; over-annotation.
GO:0043279 response to alkaloid
IEA
GO_REF:0000107 		MARK AS OVER ANNOTATED
Summary: Electronic transfer from the rat ortholog. Off-context response term with no direct mechanistic link to human CPT1A function.
Reason: Transferred response term that does not inform CPT1A's molecular function; likely over-annotation for the human gene.
GO:0045471 response to ethanol
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Electronic transfer from the rat ortholog. Ethanol modulates hepatic fatty-acid oxidation, but this is downstream physiology transferred from another species.
Reason: Plausible physiological context for a hepatic fatty-acid-oxidation enzyme but not a core function; retained as non-core.
GO:0046320 regulation of fatty acid oxidation
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Electronic transfer from the rat ortholog. CPT1A is the principal regulatory point of fatty-acid oxidation (malonyl-CoA-sensitive), consistent with a regulatory role.
Reason: CPT1A is the key regulatory node of fatty-acid oxidation, so a regulatory process annotation is defensible, but the informative statement is its catalytic role in beta-oxidation. Retained as non-core.
Supporting Evidence:
PMID:16651524
Malonyl-CoA is an established inhibitor of
GO:0050796 regulation of insulin secretion
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Electronic transfer from the rat ortholog. Fatty-acid oxidation influences beta-cell insulin secretion, but this is indirect physiology transferred across species.
Reason: Indirect physiological effect rather than a core CPT1A activity; retained as non-core.
GO:0071398 cellular response to fatty acid
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Electronic transfer from the rat ortholog. CPT1A is transcriptionally up-regulated by fatty acids (UniProt INDUCTION; PMID:16271724), consistent with responding to fatty acids.
Reason: Consistent with fatty-acid induction of CPT1A, but this is a regulatory/response context rather than the core molecular function. Retained as non-core.
GO:0097421 liver regeneration
IEA
GO_REF:0000107 		MARK AS OVER ANNOTATED
Summary: Electronic transfer from the rat ortholog. Highly indirect physiological context with no direct mechanistic tie to CPT1A's molecular function.
Reason: Liver-regeneration annotation transferred from the rat ortholog is far removed from CPT1A's molecular activity; likely over-annotation.
GO:1904772 response to tetrachloromethane
IEA
GO_REF:0000107 		MARK AS OVER ANNOTATED
Summary: Electronic transfer from the rat ortholog (a hepatotoxicant-exposure response). Off-context and does not inform CPT1A function.
Reason: Toxicant-response term transferred from the rat ortholog; does not describe CPT1A's molecular function. Likely over-annotation.
GO:0001678 intracellular glucose homeostasis
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: Sequence-similarity transfer (from mouse Cpt1a) of a glucose-homeostasis role. Reflects the indirect metabolic coupling between fatty-acid oxidation and glucose handling.
Reason: Effect on glucose homeostasis is downstream of the enzyme's fatty-acid-oxidation function rather than a direct activity; retained as non-core.
GO:0006635 fatty acid beta-oxidation
ISS
GO_REF:0000024 		ACCEPT
Summary: Sequence-similarity transfer of the fatty acid beta-oxidation process, consistent with CPT1A's role as the committed step of long-chain fatty-acid import for beta-oxidation.
Reason: Correct central process term, corroborated by IEA, TAS (PMID:7892212) and the enzyme's established biology.
Supporting Evidence:
PMID:9691089
decreased rate of fatty acid beta-oxidation
GO:0006853 carnitine shuttle
TAS
Reactome:R-HSA-200425 		ACCEPT
Summary: Reactome traceable-author-statement placing CPT1A in the carnitine shuttle pathway, where it catalyzes the initial acylcarnitine-forming step.
Reason: Accurately reflects CPT1A's role as the first, rate-limiting step of the carnitine shuttle that imports long-chain fatty acids into mitochondria.
Supporting Evidence:
PMID:16651524
controls entry of fatty acids into mitochondria and, thereby, fatty acid oxidation
GO:0004095 carnitine O-palmitoyltransferase activity
EXP
PMID:14517221
Functional and structural basis of carnitine palmitoyltransf... 		ACCEPT
Summary: Experimental characterization of CPT1A carnitine O-palmitoyltransferase activity, including kinetics and disease-variant analysis in a heterologous yeast expression system.
Reason: Directly supports the core catalytic function of CPT1A; disease-causing variants (e.g. G709E, G710E) abolish this activity, confirming its centrality.
Supporting Evidence:
PMID:14517221
mutations G709E and G710E, which abolish
GO:0005739 mitochondrion
IDA
GO_REF:0000052 		KEEP AS NON CORE
Summary: Immunofluorescence-based (HPA) localization of CPT1A to the mitochondrion. Correct but less specific than the mitochondrial outer membrane localization.
Reason: Consistent with CPT1A localization; the more specific and informative compartment is the mitochondrial outer membrane (GO:0005741). Retained as non-core parent.
GO:0004095 carnitine O-palmitoyltransferase activity
EXP
PMID:16651524
The brain-specific carnitine palmitoyltransferase-1c regulat... 		ACCEPT
Summary: Experimental comparison showing that CPT1A (liver) catalyzes acyl transfer from fatty acyl-CoAs to carnitine, in contrast to the catalytically inactive brain isoform CPT1C.
Reason: Directly supports CPT1A's carnitine O-palmitoyltransferase activity as its core molecular function.
Supporting Evidence:
PMID:16651524
CPT1a and CPT1b catalyze acyl transfer from various fatty
GO:0005741 mitochondrial outer membrane
EXP
PMID:11350182
Molecular and enzymatic characterization of a unique carniti... 		ACCEPT
Summary: Experimental determination of CPT1A subcellular location at the mitochondrial outer membrane (variant characterization also assessed mitochondrial targeting).
Reason: The mitochondrial outer membrane is the specific, correct compartment for CPT1A, consistent with the UniProt SUBCELLULAR LOCATION statement and the two-transmembrane-helix outer-membrane topology.
Supporting Evidence:
PMID:11350182
alters neither mitochondrial targeting nor stability of the CPT1A
GO:0005739 mitochondrion
HTP
PMID:34800366
Quantitative high-confidence human mitochondrial proteome an... 		KEEP AS NON CORE
Summary: High-throughput mitochondrial proteome study detecting CPT1A in the mitochondrion. Correct but less specific than the outer-membrane localization.
Reason: Supports mitochondrial localization at low specificity; the informative compartment is the mitochondrial outer membrane. Retained as non-core parent.
GO:0030674 protein-macromolecule adaptor activity
IDA
PMID:38016475
CPT1A induction following epigenetic perturbation promotes M... 		ACCEPT
Summary: CPT1A acts as an adaptor/scaffold that recruits the ER-localized palmitoyl transferase ZDHHC4 to MAVS, promoting MAVS Cys79-palmitoylation; a catalytically-dead H473A mutant retains this scaffolding activity, showing it is independent of the acyltransferase activity.
Reason: Directly demonstrated adaptor/scaffold function bridging ZDHHC4 and MAVS. This is a genuine but non-core (moonlighting) molecular function, distinct from the canonical carnitine O-palmitoyltransferase activity.
Supporting Evidence:
PMID:38016475
CPT1A recruits the endoplasmic
GO:0045089 positive regulation of innate immune response
IDA
PMID:38016475
CPT1A induction following epigenetic perturbation promotes M... 		ACCEPT
Summary: By recruiting ZDHHC4 to palmitoylate and stabilize MAVS, CPT1A sustains a double-stranded-RNA-activated type I interferon response and potentiates antitumor immunity.
Reason: Experimentally supported role in positively regulating the innate (type I IFN) immune response via MAVS stabilization; a real but non-core process for this metabolic enzyme.
Supporting Evidence:
PMID:38016475
sustains, a double-stranded
GO:0004095 carnitine O-palmitoyltransferase activity
IMP
PMID:14517221
Functional and structural basis of carnitine palmitoyltransf... 		ACCEPT
Summary: Mutant-phenotype evidence in which disease-causing missense variants (G709E, G710E) abolish CPT1A carnitine O-palmitoyltransferase activity, demonstrating the wild-type enzyme carries out this reaction.
Reason: Supports the core catalytic function through loss-of-function variant analysis; consistent with the EXP annotation from the same study.
Supporting Evidence:
PMID:14517221
mutations G709E and G710E, which abolish
GO:0004095 carnitine O-palmitoyltransferase activity
IMP
PMID:9691089
Molecular basis of hepatic carnitine palmitoyltransferase I ... 		ACCEPT
Summary: Mutant-phenotype evidence in which the disease-causing D454G variant expressed in yeast retained only ~2% of wild-type activity, establishing CPT1A's carnitine O-palmitoyltransferase activity.
Reason: Loss-of-function variant confirms the core catalytic function of CPT1A.
Supporting Evidence:
PMID:9691089
D454G mutation is the disease-causing mutation
GO:0005741 mitochondrial outer membrane
IMP
PMID:14517221
Functional and structural basis of carnitine palmitoyltransf... 		ACCEPT
Summary: Variant/expression analysis consistent with CPT1A residing at the mitochondrial outer membrane.
Reason: Supports the specific, correct mitochondrial outer membrane localization, concordant with the EXP and ISS annotations to the same term.
Supporting Evidence:
PMID:16651524
an outer mitochondrial membrane enzyme
GO:0016020 membrane
HDA
PMID:19946888
Defining the membrane proteome of NK cells. 		MARK AS OVER ANNOTATED
Summary: High-throughput membrane-proteome detection of CPT1A in an NK-like cell line. Correct at a very general level (CPT1A is a membrane protein) but off-context and uninformative.
Reason: CPT1A is indeed a membrane protein, but membrane is a very general term and this detection comes from an unrelated NK-cell membrane proteomics screen; the informative localization is the mitochondrial outer membrane.
GO:0004095 carnitine O-palmitoyltransferase activity
IDA
PMID:7892212
Human liver mitochondrial carnitine palmitoyltransferase I: ... 		ACCEPT
Summary: Characterization of the cloned human liver CPT I cDNA/enzyme, establishing it as a carnitine palmitoyltransferase (EC 2.3.1.21) distinct from CPT II.
Reason: Foundational characterization supporting the core carnitine O-palmitoyltransferase activity of human CPT1A.
Supporting Evidence:
PMID:7892212
Human liver mitochondrial carnitine palmitoyltransferase I
GO:0030855 epithelial cell differentiation
IEP
PMID:21492153
Analysis of proteomic changes induced upon cellular differen... 		MARK AS OVER ANNOTATED
Summary: Expression-pattern evidence in which CPT1A was among lipid-metabolism proteins up-regulated during differentiation of the Caco-2 intestinal cell line. This is a correlative association, not a demonstrated role in differentiation.
Reason: The IEP annotation reflects a correlative change in CPT1A abundance during Caco-2 differentiation, not evidence that CPT1A drives epithelial cell differentiation; likely over-annotation.
Supporting Evidence:
PMID:21492153
proteins involved in xenobiotic and drug metabolism as well as in lipid metabolism were upregulated upon cellular differentiation
GO:0005741 mitochondrial outer membrane
TAS
Reactome:R-HSA-200406 		ACCEPT
Summary: Reactome traceable-author-statement placing CPT1A at the mitochondrial outer membrane, where it transfers palmitoyl to carnitine.
Reason: Concordant with the experimentally established mitochondrial outer membrane localization; correct and specific.
Supporting Evidence:
PMID:16651524
an outer mitochondrial membrane enzyme
GO:0001676 long-chain fatty acid metabolic process
IDA
PMID:11350182
Molecular and enzymatic characterization of a unique carniti... 		ACCEPT
Summary: Direct-assay evidence of CPT1A's role in long-chain fatty acid metabolism, consistent with its substrate specificity for long-chain acyl-CoAs.
Reason: Correct, specific process term supported by direct experimental characterization of the enzyme.
Supporting Evidence:
PMID:11350182
a rare disorder
GO:0004095 carnitine O-palmitoyltransferase activity
IDA
PMID:11350182
Molecular and enzymatic characterization of a unique carniti... 		ACCEPT
Summary: Direct kinetic characterization of CPT1A carnitine O-palmitoyltransferase activity (KM/Vmax for carnitine and palmitoyl-CoA), with the G710E variant shown to be catalytically inactive.
Reason: Direct experimental support for the core catalytic function of CPT1A.
Supporting Evidence:
PMID:11350182
CPT1A is totally inactive
GO:0005739 mitochondrion
IDA
PMID:11350182
Molecular and enzymatic characterization of a unique carniti... 		KEEP AS NON CORE
Summary: Direct evidence that CPT1A localizes to the mitochondrion (mitochondrial targeting assessed for the G710E variant). Correct but less specific than the outer membrane.
Reason: Supports mitochondrial localization; the informative compartment is the mitochondrial outer membrane (GO:0005741). Retained as non-core parent.
Supporting Evidence:
PMID:11350182
alters neither mitochondrial targeting nor stability of the CPT1A
GO:0005741 mitochondrial outer membrane
ISS
GO_REF:0000024 		ACCEPT
Summary: Sequence-similarity transfer (from rat Cpt1a, P32198) of the mitochondrial outer membrane localization, consistent with the human experimental data.
Reason: Correct, specific compartment concordant with the human EXP/IMP annotations.
Supporting Evidence:
PMID:16651524
an outer mitochondrial membrane enzyme
GO:0009437 carnitine metabolic process
IDA
PMID:11350182
Molecular and enzymatic characterization of a unique carniti... 		ACCEPT
Summary: Direct-assay evidence for CPT1A's role in carnitine metabolism, consistent with its use of L-carnitine as the acyl acceptor.
Reason: Correct process term supported by direct experimental characterization.
Supporting Evidence:
PMID:11350182
a rare disorder
GO:0004095 carnitine O-palmitoyltransferase activity
TAS
PMID:7892212
Human liver mitochondrial carnitine palmitoyltransferase I: ... 		ACCEPT
Summary: Traceable-author-statement citing characterization of the human liver CPT I enzyme (EC 2.3.1.21).
Reason: Supports the core carnitine O-palmitoyltransferase activity of CPT1A.
Supporting Evidence:
PMID:7892212
Human liver mitochondrial carnitine palmitoyltransferase I
GO:0005739 mitochondrion
TAS
PMID:7892212
Human liver mitochondrial carnitine palmitoyltransferase I: ... 		KEEP AS NON CORE
Summary: Traceable-author-statement for mitochondrial localization of the human liver CPT I. Correct but general.
Reason: Supports mitochondrial localization at low specificity; outer membrane is the informative compartment. Retained as non-core parent.
Supporting Evidence:
PMID:7892212
Human liver mitochondrial carnitine palmitoyltransferase I
GO:0006635 fatty acid beta-oxidation
TAS
PMID:7892212
Human liver mitochondrial carnitine palmitoyltransferase I: ... 		ACCEPT
Summary: Traceable-author-statement placing human liver CPT I in mitochondrial fatty acid beta-oxidation, where it catalyzes the committed import step.
Reason: Correct, central process term consistent with CPT1A biology and corroborated by IEA/ISS annotations.
Supporting Evidence:
PMID:7892212
Human liver mitochondrial carnitine palmitoyltransferase I

Core Functions

Catalyzes the rate-limiting, malonyl-CoA-inhibited transfer of long-chain acyl groups from acyl-CoA thioesters to L-carnitine at the mitochondrial outer membrane, forming long-chain acylcarnitine and CoA and committing long-chain fatty acids to mitochondrial import and beta-oxidation.

Molecular Function:
carnitine O-palmitoyltransferase activity
Directly Involved In:
fatty acid beta-oxidation carnitine shuttle long-chain fatty acid metabolic process
Cellular Locations:
mitochondrial outer membrane
Supporting Evidence:
  • PMID:14517221
    Carnitine palmitoyltransferase 1A (CPT1A) is the
  • PMID:16651524
    controls entry of fatty acids into mitochondria and, thereby, fatty acid oxidation

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000024
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
GO_REF:0000033
Annotation inferences using phylogenetic trees
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:0000117
Electronic Gene Ontology annotations created by ARBA machine learning models
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
PMID:11350182
Molecular and enzymatic characterization of a unique carnitine palmitoyltransferase 1A mutation in the Hutterite community.
PMID:14517221
Functional and structural basis of carnitine palmitoyltransferase 1A deficiency.
PMID:16651524
The brain-specific carnitine palmitoyltransferase-1c regulates energy homeostasis.
PMID:19946888
Defining the membrane proteome of NK cells.
PMID:21492153
Analysis of proteomic changes induced upon cellular differentiation of the human intestinal cell line Caco-2.
PMID:34800366
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
PMID:38016475
CPT1A induction following epigenetic perturbation promotes MAVS palmitoylation and activation to potentiate antitumor immunity.
PMID:7892212
Human liver mitochondrial carnitine palmitoyltransferase I: characterization of its cDNA and chromosomal localization and partial analysis of the gene.
PMID:9691089
Molecular basis of hepatic carnitine palmitoyltransferase I deficiency.
Reactome:R-HSA-200406
CPT1A transfers PALM to CAR
Reactome:R-HSA-200425
Carnitine shuttle

📚 Additional Documentation

Notes

(CPT1A-notes.md)

CPT1A (P50416) review notes

Deep research status

just deep-research human CPT1A --provider falcon did NOT produce a
CPT1A-deep-research-falcon.md file within the polling window (the running
deep-research-client process on the machine was for CPT2, a concurrent batch job,
not CPT1A). Review therefore grounded in CPT1A-uniprot.txt (UniProt P50416,
entry v221) and cached publications/PMID_*.md. No -deep-research-*.md file was
fabricated (per policy).

Verified biology (UniProt P50416 + primary literature)

  • RecName: Carnitine O-palmitoyltransferase 1, liver isoform (Short CPT1-L);
    AltName CPT I, liver isoform; AltName Carnitine palmitoyltransferase 1A;
    AltName Succinyltransferase CPT1A. EC 2.3.1.21.
  • Liver isoform of CPT1. Catalyses the committed, rate-limiting step of long-chain
    fatty-acid import for mitochondrial beta-oxidation: transfer of a long-chain acyl
    group from acyl-CoA to L-carnitine, giving long-chain acylcarnitine + CoA
    (RHEA:12661; (R)-carnitine + hexadecanoyl-CoA = O-hexadecanoyl-(R)-carnitine + CoA).
  • Location: mitochondrion outer membrane, multi-pass membrane protein
    (TOPO_DOM/TRANSMEM: two TM helices 48-73, 103-122; large C-terminal cytoplasmic
    catalytic domain 123-773). Confirmed EXP in PubMed:11350182, PubMed:14517221.
  • Key regulatory point of fatty-acid oxidation; allosterically inhibited by
    malonyl-CoA     (ACTIVITY REGULATION, PubMed:14517221; N-terminal 1-42 conformational
    switch, PubMed:21990363/PDB 2LE3).
  • Deficiency: CPT1A deficiency (CPT1AD, MIM:255120) — autosomal recessive
    hypoketotic hypoglycemia; many characterised loss-of-function variants
    (D454G, G709E, G710E, etc.).
  • Secondary/moonlighting functions (from UniProt + primary papers):
  • Lysine succinyltransferase activity (EC 2.3.1.-; succinyl-CoA + protein Lys),
    e.g. on ENO1, independent of the O-palmitoyltransferase activity
    (PubMed:29425493 — NOT cached).
  • Scaffold/adaptor: recruits ER-localized ZDHHC4 to palmitoylate MAVS
    (Cys79) at mitochondria, stabilising/activating MAVS and sustaining the
    type-I IFN response / antitumor immunity; catalytically-dead H473A retains this
    scaffolding activity (PubMed:38016475). This underlies the
    protein-macromolecule adaptor activity (GO:0030674) and positive regulation of
    innate immune response (GO:0045089) IDA annotations.

Annotation review decisions (summary)

  • Core MF GO:0004095 carnitine O-palmitoyltransferase activity: ACCEPT (EXP/IDA/IBA;
    multiple: PMID:11350182 IDA, PMID:7892212 IDA/TAS, PMID:14517221 EXP/IMP,
    PMID:16651524 EXP, PMID:9691089 IMP). Core function.
  • CC mitochondrial outer membrane (GO:0005741): ACCEPT (EXP PMID:11350182, IMP
    PMID:14517221, plus ISS/IEA/TAS). This is the specific correct compartment.
  • CC mitochondrion (GO:0005739) IBA/IDA/HTP/TAS: less specific than outer membrane;
    KEEP_AS_NON_CORE (redundant parent).
  • CC membrane (GO:0016020) HDA PMID:19946888 (NK cell membrane proteome): correct
    but very general and off-context; MARK_AS_OVER_ANNOTATED.
  • BP fatty acid beta-oxidation (GO:0006635), carnitine shuttle (GO:0006853),
    long-chain fatty acid metabolic process (GO:0001676), carnitine metabolic process
    (GO:0009437): ACCEPT — directly informed by function; these + fatty acid metabolic
    process (GO:0006631, parent, KEEP_AS_NON_CORE) frame the core process.
  • MF acyltransferase activity (GO:0016746) IEA InterPro: correct but general parent
    of GO:0004095; MARK_AS_OVER_ANNOTATED / could MODIFY to GO:0004095.
  • BP positive regulation of innate immune response (GO:0045089) IDA + MF
    protein-macromolecule adaptor activity (GO:0030674) IDA (PMID:38016475): ACCEPT
    as real but non-core moonlighting scaffold function (MAVS/ZDHHC4). Kept out of
    core_functions location claims (mito outer surface vs ER contact unresolved).
  • Ensembl GO_REF:0000107 rat-ortholog IEA physiology terms (response to hypoxia,
    glucose metabolic process, triglyceride metabolic process, response to nutrient,
    response to xenobiotic, response to nutrient levels, eating behavior, response to
    alkaloid, response to ethanol, regulation of insulin secretion, cellular response
    to fatty acid, liver regeneration, response to tetrachloromethane, identical
    protein binding, positive regulation of fatty acid beta-oxidation, regulation of
    fatty acid oxidation): mostly downstream physiology / rat-transferred; kept as
    KEEP_AS_NON_CORE or MARK_AS_OVER_ANNOTATED individually. identical protein binding is uninformative -> MARK_AS_OVER_ANNOTATED. positive regulation of fatty acid beta-oxidation (a positive-regulation term for the enzyme itself) is
    arguably a self-referential over-call -> MARK_AS_OVER_ANNOTATED; the plain
    regulation of fatty acid oxidation retained NON_CORE (malonyl-CoA is CPT1's
    own regulator, not CPT1 regulating others).
  • GO:0006006 glucose metabolic process / GO:0001678 intracellular glucose
    homeostasis (ISS from mouse): indirect physiology, KEEP_AS_NON_CORE.
  • GO:0030855 epithelial cell differentiation IEP PMID:21492153 (Caco-2 proteomics,
    CPT1A up on differentiation): correlative only; MARK_AS_OVER_ANNOTATED.

core_functions

  1. MF GO:0004095 carnitine O-palmitoyltransferase activity; directly involved in
    fatty acid beta-oxidation (GO:0006635), carnitine shuttle (GO:0006853),
    long-chain fatty acid metabolic process (GO:0001676); located in mitochondrial
    outer membrane (GO:0005741).

📄 View Raw YAML

 
id: P50416
gene_symbol: CPT1A
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: Carnitine O-palmitoyltransferase 1, liver isoform (CPT1A) is the liver-type
  isoform of carnitine palmitoyltransferase 1, a multi-pass protein of the mitochondrial
  outer membrane with a large cytoplasmic C-terminal catalytic domain. It catalyzes
  the committed, rate-limiting step of long-chain fatty acid entry into mitochondria
  for beta-oxidation, transferring the acyl group of long-chain acyl-CoA thioesters
  (e.g. palmitoyl-CoA) onto L-carnitine to form long-chain acylcarnitine plus CoA
  (EC 2.3.1.21). As the principal regulatory node of the carnitine shuttle, its activity
  is allosterically inhibited by malonyl-CoA, coupling fatty-acid oxidation to fatty-acid
  synthesis and nutritional state. Loss-of-function variants cause carnitine palmitoyltransferase
  1A deficiency, an autosomal recessive disorder of fatty-acid oxidation presenting
  with hypoketotic hypoglycemia. Beyond its canonical acyltransferase role, CPT1A
  has reported secondary activities, including a lysine succinyltransferase activity
  and a catalysis-independent scaffolding function that recruits ZDHHC4 to promote
  MAVS palmitoylation and sustain the type I interferon response.
alternative_products:
- name: '1'
  id: P50416-1
- name: '2'
  id: P50416-2
  sequence_note: VSP_012167
existing_annotations:
- term:
    id: GO:0004095
    label: carnitine O-palmitoyltransferase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Phylogenetic (IBA) assignment of the defining molecular function of CPT1A,
      transfer of a long-chain acyl group from acyl-CoA to carnitine. This is strongly
      supported by direct experimental characterization of the human enzyme and is
      the core function of the gene.
    action: ACCEPT
    reason: The carnitine O-palmitoyltransferase activity (EC 2.3.1.21) is the well-established
      catalytic function of CPT1A and is the correct level of specificity. It is corroborated
      by multiple experimental annotations in this dataset.
    supported_by:
    - reference_id: PMID:14517221
      supporting_text: Carnitine palmitoyltransferase 1A (CPT1A) is the
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetic assignment placing CPT1A activity in the mitochondrion.
      Correct but less specific than the experimentally supported mitochondrial outer
      membrane localization.
    action: KEEP_AS_NON_CORE
    reason: The mitochondrion is a true but general compartment; the specific and
      informative localization is the mitochondrial outer membrane (GO:0005741), which
      is captured by experimental annotations. Retained as non-core parent term.
    supported_by:
    - reference_id: PMID:11350182
      supporting_text: alters neither mitochondrial targeting nor stability of the
        CPT1A
- term:
    id: GO:0006631
    label: fatty acid metabolic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetic assignment of a general fatty acid metabolic role. True
      but a broad parent of the more specific beta-oxidation / long-chain fatty acid
      metabolic terms.
    action: KEEP_AS_NON_CORE
    reason: CPT1A is genuinely involved in fatty acid metabolism, but this term is
      a general parent; the specific process is long-chain fatty acid import for beta-oxidation
      (GO:0006635, GO:0001676). Kept as non-core.
    supported_by:
    - reference_id: PMID:14517221
      supporting_text: key regulatory enzyme of
- term:
    id: GO:0009437
    label: carnitine metabolic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetic assignment of a carnitine metabolic role, consistent with
      CPT1A producing acylcarnitine from carnitine as part of the carnitine shuttle.
    action: ACCEPT
    reason: CPT1A consumes L-carnitine to generate long-chain acylcarnitine, directly
      participating in carnitine metabolism; supported experimentally (PMID:11350182,
      IDA in this dataset).
    supported_by:
    - reference_id: PMID:14517221
      supporting_text: Carnitine palmitoyltransferase 1A (CPT1A) is the
- term:
    id: GO:0004095
    label: carnitine O-palmitoyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Electronic assignment (ARBA/RHEA/EC 2.3.1.21) of the core carnitine O-palmitoyltransferase
      activity, matching the experimentally established function.
    action: ACCEPT
    reason: Correct and specific molecular function, consistent with the RHEA:12661
      reaction and EC 2.3.1.21 in the UniProt record and multiple experimental annotations.
    supported_by:
    - reference_id: PMID:14517221
      supporting_text: Carnitine palmitoyltransferase 1A (CPT1A) is the
- term:
    id: GO:0005741
    label: mitochondrial outer membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: Electronic assignment of the mitochondrial outer membrane localization,
      matching the experimentally verified subcellular location of CPT1A.
    action: ACCEPT
    reason: The mitochondrial outer membrane is the correct, specific compartment
      for CPT1A and is supported experimentally (PMID:11350182, PMID:14517221) and
      by the UniProt SUBCELLULAR LOCATION statement.
    supported_by:
    - reference_id: PMID:16651524
      supporting_text: an outer mitochondrial membrane enzyme
- term:
    id: GO:0006853
    label: carnitine shuttle
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: Electronic (ARBA) assignment of the carnitine shuttle process. CPT1A
      catalyzes the first, committed step of the carnitine shuttle that imports long-chain
      fatty acids into mitochondria.
    action: ACCEPT
    reason: CPT1A performs the rate-limiting acylcarnitine-forming step of the carnitine
      shuttle; a correct and specific process term. Corroborated by the Reactome TAS
      annotation to the same term.
    supported_by:
    - reference_id: PMID:16651524
      supporting_text: controls entry of fatty acids into mitochondria and, thereby,
        fatty acid oxidation
- term:
    id: GO:0016746
    label: acyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro-based electronic assignment of the general acyltransferase activity
      (from the carnitine acyltransferase domain IPR000542). This is a broad parent
      of the specific carnitine O-palmitoyltransferase activity.
    action: MARK_AS_OVER_ANNOTATED
    reason: Not wrong, but a general parent of GO:0004095 which is annotated more
      precisely. The specific carnitine O-palmitoyltransferase activity should be
      preferred as the informative molecular function.
    proposed_replacement_terms:
    - id: GO:0004095
      label: carnitine O-palmitoyltransferase activity
- term:
    id: GO:0001666
    label: response to hypoxia
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Electronic transfer of a rat-ortholog phenotype/expression annotation.
      Reflects downstream physiology rather than CPT1A's molecular function.
    action: KEEP_AS_NON_CORE
    reason: Response to hypoxia is a plausible physiological context for fatty-acid
      oxidation regulation but is transferred from the rat ortholog and is not a core
      molecular activity of CPT1A. Retained as non-core.
- term:
    id: GO:0001676
    label: long-chain fatty acid metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Electronic assignment of long-chain fatty acid metabolic process, matching
      the substrate specificity of CPT1A (long-chain acyl-CoA thioesters).
    action: ACCEPT
    reason: CPT1A acts specifically on long-chain acyl-CoA substrates to enable their
      mitochondrial oxidation; this specific process term is well supported (also
      IDA PMID:11350182 in this dataset).
    supported_by:
    - reference_id: PMID:14517221
      supporting_text: hepatic long-chain fatty acid beta-oxidation
- term:
    id: GO:0006006
    label: glucose metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Electronic transfer from the rat ortholog. Reflects the indirect metabolic
      influence of fatty-acid oxidation on glucose handling rather than a direct role.
    action: KEEP_AS_NON_CORE
    reason: Any effect on glucose metabolism is downstream/indirect (fatty-acid oxidation
      spares glucose); not a core CPT1A function. Retained as non-core.
- term:
    id: GO:0006631
    label: fatty acid metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Electronic assignment of the general fatty acid metabolic process, duplicating
      the IBA annotation to the same broad parent term.
    action: KEEP_AS_NON_CORE
    reason: True but general; the specific process is long-chain fatty acid import
      for beta-oxidation. Kept as non-core parent.
- term:
    id: GO:0006635
    label: fatty acid beta-oxidation
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: Electronic assignment (ARBA/UniPathway UPA00659) of fatty acid beta-oxidation.
      CPT1A catalyzes the rate-limiting import step required for mitochondrial beta-oxidation
      of long-chain fatty acids.
    action: ACCEPT
    reason: CPT1A is the committed step controlling long-chain fatty-acid entry for
      beta-oxidation; a correct and central process term, corroborated by TAS (PMID:7892212)
      and ISS annotations.
    supported_by:
    - reference_id: PMID:9691089
      supporting_text: decreased rate of fatty acid beta-oxidation
- term:
    id: GO:0006641
    label: triglyceride metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Electronic transfer from the rat ortholog. UniProt notes a role in hepatic
      triglyceride metabolism (by similarity), but this is a downstream/indirect physiological
      consequence.
    action: KEEP_AS_NON_CORE
    reason: Consistent with a hepatic triglyceride-metabolism role inferred by similarity,
      but indirect relative to the core acyltransferase function. Retained as non-core.
- term:
    id: GO:0007584
    label: response to nutrient
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Electronic transfer from the rat ortholog capturing nutritional regulation
      of CPT1A/fatty-acid oxidation.
    action: KEEP_AS_NON_CORE
    reason: Reflects physiological regulation (CPT1A is induced by fatty acids and
      regulated by nutritional state) rather than a core molecular function. Retained
      as non-core.
- term:
    id: GO:0009410
    label: response to xenobiotic stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Electronic transfer from the rat ortholog. Off-context response term
      with no direct mechanistic link to CPT1A's function established for human.
    action: MARK_AS_OVER_ANNOTATED
    reason: Xenobiotic-response annotation transferred from the rat ortholog does
      not inform CPT1A's molecular function and is a likely over-annotation for the
      human gene.
- term:
    id: GO:0009437
    label: carnitine metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Electronic assignment of carnitine metabolic process, duplicating the
      IBA/IDA annotations. Consistent with CPT1A consuming carnitine to form acylcarnitine.
    action: ACCEPT
    reason: CPT1A directly participates in carnitine metabolism as part of the carnitine
      shuttle; correct process term corroborated by experimental (IDA) evidence.
    supported_by:
    - reference_id: PMID:16651524
      supporting_text: catalyze acyl transfer from various fatty
- term:
    id: GO:0031667
    label: response to nutrient levels
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Electronic transfer from the rat ortholog capturing regulation by nutritional
      state (fasting/feeding).
    action: KEEP_AS_NON_CORE
    reason: Reflects physiological regulation of CPT1A rather than its core molecular
      activity. Retained as non-core.
- term:
    id: GO:0032000
    label: positive regulation of fatty acid beta-oxidation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Electronic transfer from the rat ortholog. CPT1A is the enzyme that carries
      out the rate-limiting step of beta-oxidation; framing this as CPT1A positively
      regulating beta-oxidation is largely self-referential.
    action: MARK_AS_OVER_ANNOTATED
    reason: CPT1A executes the committed step of long-chain beta-oxidation (captured
      by GO:0006635); a separate positive-regulation term for the enzyme regulating
      the very process it catalyzes is an over-annotation.
- term:
    id: GO:0042755
    label: eating behavior
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Electronic transfer from the rat ortholog. Eating-behavior/energy-homeostasis
      roles are best established for the brain isoform CPT1C, not the liver CPT1A.
    action: MARK_AS_OVER_ANNOTATED
    reason: Feeding-behavior control via malonyl-CoA sensing is chiefly attributed
      to the brain-specific CPT1C (PMID:16651524); assigning eating behavior to liver
      CPT1A by ortholog transfer is a likely over-annotation.
    supported_by:
    - reference_id: PMID:16651524
      supporting_text: CPT1c KO mice have lower body weight and food intake
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: Electronic transfer from the rat ortholog of self-association. CPT1A
      is reported to form homo-oligomers (homohexamer/homotrimer, by similarity),
      but the bare identical protein binding term is uninformative about function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Although CPT1A oligomerizes, identical protein binding is an uninformative
      binding term that does not describe a molecular function; over-annotation.
- term:
    id: GO:0043279
    label: response to alkaloid
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Electronic transfer from the rat ortholog. Off-context response term
      with no direct mechanistic link to human CPT1A function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Transferred response term that does not inform CPT1A's molecular function;
      likely over-annotation for the human gene.
- term:
    id: GO:0045471
    label: response to ethanol
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Electronic transfer from the rat ortholog. Ethanol modulates hepatic
      fatty-acid oxidation, but this is downstream physiology transferred from another
      species.
    action: KEEP_AS_NON_CORE
    reason: Plausible physiological context for a hepatic fatty-acid-oxidation enzyme
      but not a core function; retained as non-core.
- term:
    id: GO:0046320
    label: regulation of fatty acid oxidation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Electronic transfer from the rat ortholog. CPT1A is the principal regulatory
      point of fatty-acid oxidation (malonyl-CoA-sensitive), consistent with a regulatory
      role.
    action: KEEP_AS_NON_CORE
    reason: CPT1A is the key regulatory node of fatty-acid oxidation, so a regulatory
      process annotation is defensible, but the informative statement is its catalytic
      role in beta-oxidation. Retained as non-core.
    supported_by:
    - reference_id: PMID:16651524
      supporting_text: Malonyl-CoA is an established inhibitor of
- term:
    id: GO:0050796
    label: regulation of insulin secretion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Electronic transfer from the rat ortholog. Fatty-acid oxidation influences
      beta-cell insulin secretion, but this is indirect physiology transferred across
      species.
    action: KEEP_AS_NON_CORE
    reason: Indirect physiological effect rather than a core CPT1A activity; retained
      as non-core.
- term:
    id: GO:0071398
    label: cellular response to fatty acid
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Electronic transfer from the rat ortholog. CPT1A is transcriptionally
      up-regulated by fatty acids (UniProt INDUCTION; PMID:16271724), consistent with
      responding to fatty acids.
    action: KEEP_AS_NON_CORE
    reason: Consistent with fatty-acid induction of CPT1A, but this is a regulatory/response
      context rather than the core molecular function. Retained as non-core.
- term:
    id: GO:0097421
    label: liver regeneration
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Electronic transfer from the rat ortholog. Highly indirect physiological
      context with no direct mechanistic tie to CPT1A's molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Liver-regeneration annotation transferred from the rat ortholog is far
      removed from CPT1A's molecular activity; likely over-annotation.
- term:
    id: GO:1904772
    label: response to tetrachloromethane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Electronic transfer from the rat ortholog (a hepatotoxicant-exposure
      response). Off-context and does not inform CPT1A function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Toxicant-response term transferred from the rat ortholog; does not describe
      CPT1A's molecular function. Likely over-annotation.
- term:
    id: GO:0001678
    label: intracellular glucose homeostasis
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Sequence-similarity transfer (from mouse Cpt1a) of a glucose-homeostasis
      role. Reflects the indirect metabolic coupling between fatty-acid oxidation
      and glucose handling.
    action: KEEP_AS_NON_CORE
    reason: Effect on glucose homeostasis is downstream of the enzyme's fatty-acid-oxidation
      function rather than a direct activity; retained as non-core.
- term:
    id: GO:0006635
    label: fatty acid beta-oxidation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Sequence-similarity transfer of the fatty acid beta-oxidation process,
      consistent with CPT1A's role as the committed step of long-chain fatty-acid
      import for beta-oxidation.
    action: ACCEPT
    reason: Correct central process term, corroborated by IEA, TAS (PMID:7892212)
      and the enzyme's established biology.
    supported_by:
    - reference_id: PMID:9691089
      supporting_text: decreased rate of fatty acid beta-oxidation
- term:
    id: GO:0006853
    label: carnitine shuttle
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-200425
  qualifier: involved_in
  review:
    summary: Reactome traceable-author-statement placing CPT1A in the carnitine shuttle
      pathway, where it catalyzes the initial acylcarnitine-forming step.
    action: ACCEPT
    reason: Accurately reflects CPT1A's role as the first, rate-limiting step of the
      carnitine shuttle that imports long-chain fatty acids into mitochondria.
    supported_by:
    - reference_id: PMID:16651524
      supporting_text: controls entry of fatty acids into mitochondria and, thereby,
        fatty acid oxidation
- term:
    id: GO:0004095
    label: carnitine O-palmitoyltransferase activity
  evidence_type: EXP
  original_reference_id: PMID:14517221
  qualifier: enables
  review:
    summary: Experimental characterization of CPT1A carnitine O-palmitoyltransferase
      activity, including kinetics and disease-variant analysis in a heterologous
      yeast expression system.
    action: ACCEPT
    reason: Directly supports the core catalytic function of CPT1A; disease-causing
      variants (e.g. G709E, G710E) abolish this activity, confirming its centrality.
    supported_by:
    - reference_id: PMID:14517221
      supporting_text: mutations G709E and G710E, which abolish
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Immunofluorescence-based (HPA) localization of CPT1A to the mitochondrion.
      Correct but less specific than the mitochondrial outer membrane localization.
    action: KEEP_AS_NON_CORE
    reason: Consistent with CPT1A localization; the more specific and informative
      compartment is the mitochondrial outer membrane (GO:0005741). Retained as non-core
      parent.
- term:
    id: GO:0004095
    label: carnitine O-palmitoyltransferase activity
  evidence_type: EXP
  original_reference_id: PMID:16651524
  qualifier: enables
  review:
    summary: Experimental comparison showing that CPT1A (liver) catalyzes acyl transfer
      from fatty acyl-CoAs to carnitine, in contrast to the catalytically inactive
      brain isoform CPT1C.
    action: ACCEPT
    reason: Directly supports CPT1A's carnitine O-palmitoyltransferase activity as
      its core molecular function.
    supported_by:
    - reference_id: PMID:16651524
      supporting_text: CPT1a and CPT1b catalyze acyl transfer from various fatty
- term:
    id: GO:0005741
    label: mitochondrial outer membrane
  evidence_type: EXP
  original_reference_id: PMID:11350182
  qualifier: located_in
  review:
    summary: Experimental determination of CPT1A subcellular location at the mitochondrial
      outer membrane (variant characterization also assessed mitochondrial targeting).
    action: ACCEPT
    reason: The mitochondrial outer membrane is the specific, correct compartment
      for CPT1A, consistent with the UniProt SUBCELLULAR LOCATION statement and the
      two-transmembrane-helix outer-membrane topology.
    supported_by:
    - reference_id: PMID:11350182
      supporting_text: alters neither mitochondrial targeting nor stability of the
        CPT1A
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HTP
  original_reference_id: PMID:34800366
  qualifier: located_in
  review:
    summary: High-throughput mitochondrial proteome study detecting CPT1A in the mitochondrion.
      Correct but less specific than the outer-membrane localization.
    action: KEEP_AS_NON_CORE
    reason: Supports mitochondrial localization at low specificity; the informative
      compartment is the mitochondrial outer membrane. Retained as non-core parent.
- term:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  evidence_type: IDA
  original_reference_id: PMID:38016475
  qualifier: enables
  review:
    summary: CPT1A acts as an adaptor/scaffold that recruits the ER-localized palmitoyl
      transferase ZDHHC4 to MAVS, promoting MAVS Cys79-palmitoylation; a catalytically-dead
      H473A mutant retains this scaffolding activity, showing it is independent of
      the acyltransferase activity.
    action: ACCEPT
    reason: Directly demonstrated adaptor/scaffold function bridging ZDHHC4 and MAVS.
      This is a genuine but non-core (moonlighting) molecular function, distinct from
      the canonical carnitine O-palmitoyltransferase activity.
    supported_by:
    - reference_id: PMID:38016475
      supporting_text: CPT1A recruits the endoplasmic
- term:
    id: GO:0045089
    label: positive regulation of innate immune response
  evidence_type: IDA
  original_reference_id: PMID:38016475
  qualifier: involved_in
  review:
    summary: By recruiting ZDHHC4 to palmitoylate and stabilize MAVS, CPT1A sustains
      a double-stranded-RNA-activated type I interferon response and potentiates antitumor
      immunity.
    action: ACCEPT
    reason: Experimentally supported role in positively regulating the innate (type
      I IFN) immune response via MAVS stabilization; a real but non-core process for
      this metabolic enzyme.
    supported_by:
    - reference_id: PMID:38016475
      supporting_text: sustains, a double-stranded
- term:
    id: GO:0004095
    label: carnitine O-palmitoyltransferase activity
  evidence_type: IMP
  original_reference_id: PMID:14517221
  qualifier: enables
  review:
    summary: Mutant-phenotype evidence in which disease-causing missense variants
      (G709E, G710E) abolish CPT1A carnitine O-palmitoyltransferase activity, demonstrating
      the wild-type enzyme carries out this reaction.
    action: ACCEPT
    reason: Supports the core catalytic function through loss-of-function variant
      analysis; consistent with the EXP annotation from the same study.
    supported_by:
    - reference_id: PMID:14517221
      supporting_text: mutations G709E and G710E, which abolish
- term:
    id: GO:0004095
    label: carnitine O-palmitoyltransferase activity
  evidence_type: IMP
  original_reference_id: PMID:9691089
  qualifier: enables
  review:
    summary: Mutant-phenotype evidence in which the disease-causing D454G variant
      expressed
      in yeast retained only ~2% of wild-type activity, establishing CPT1A's carnitine
      O-palmitoyltransferase activity.
    action: ACCEPT
    reason: Loss-of-function variant confirms the core catalytic function of CPT1A.
    supported_by:
    - reference_id: PMID:9691089
      supporting_text: D454G mutation is the disease-causing mutation
- term:
    id: GO:0005741
    label: mitochondrial outer membrane
  evidence_type: IMP
  original_reference_id: PMID:14517221
  qualifier: located_in
  review:
    summary: Variant/expression analysis consistent with CPT1A residing at the mitochondrial
      outer membrane.
    action: ACCEPT
    reason: Supports the specific, correct mitochondrial outer membrane localization,
      concordant with the EXP and ISS annotations to the same term.
    supported_by:
    - reference_id: PMID:16651524
      supporting_text: an outer mitochondrial membrane enzyme
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  qualifier: located_in
  review:
    summary: High-throughput membrane-proteome detection of CPT1A in an NK-like cell
      line. Correct at a very general level (CPT1A is a membrane protein) but off-context
      and uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: CPT1A is indeed a membrane protein, but membrane is a very general term
      and this detection comes from an unrelated NK-cell membrane proteomics screen;
      the informative localization is the mitochondrial outer membrane.
- term:
    id: GO:0004095
    label: carnitine O-palmitoyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:7892212
  qualifier: enables
  review:
    summary: Characterization of the cloned human liver CPT I cDNA/enzyme, establishing
      it as a carnitine palmitoyltransferase (EC 2.3.1.21) distinct from CPT II.
    action: ACCEPT
    reason: Foundational characterization supporting the core carnitine O-palmitoyltransferase
      activity of human CPT1A.
    supported_by:
    - reference_id: PMID:7892212
      supporting_text: Human liver mitochondrial carnitine palmitoyltransferase I
- term:
    id: GO:0030855
    label: epithelial cell differentiation
  evidence_type: IEP
  original_reference_id: PMID:21492153
  qualifier: involved_in
  review:
    summary: Expression-pattern evidence in which CPT1A was among lipid-metabolism
      proteins
      up-regulated during differentiation of the Caco-2 intestinal cell line. This
      is a correlative association, not a demonstrated role in differentiation.
    action: MARK_AS_OVER_ANNOTATED
    reason: The IEP annotation reflects a correlative change in CPT1A abundance during
      Caco-2 differentiation, not evidence that CPT1A drives epithelial cell differentiation;
      likely over-annotation.
    supported_by:
    - reference_id: PMID:21492153
      supporting_text: proteins involved in xenobiotic and drug metabolism as well
        as in lipid metabolism were upregulated upon cellular differentiation
- term:
    id: GO:0005741
    label: mitochondrial outer membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-200406
  qualifier: located_in
  review:
    summary: Reactome traceable-author-statement placing CPT1A at the mitochondrial
      outer membrane, where it transfers palmitoyl to carnitine.
    action: ACCEPT
    reason: Concordant with the experimentally established mitochondrial outer membrane
      localization; correct and specific.
    supported_by:
    - reference_id: PMID:16651524
      supporting_text: an outer mitochondrial membrane enzyme
- term:
    id: GO:0001676
    label: long-chain fatty acid metabolic process
  evidence_type: IDA
  original_reference_id: PMID:11350182
  qualifier: involved_in
  review:
    summary: Direct-assay evidence of CPT1A's role in long-chain fatty acid metabolism,
      consistent with its substrate specificity for long-chain acyl-CoAs.
    action: ACCEPT
    reason: Correct, specific process term supported by direct experimental characterization
      of the enzyme.
    supported_by:
    - reference_id: PMID:11350182
      supporting_text: a rare disorder
- term:
    id: GO:0004095
    label: carnitine O-palmitoyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:11350182
  qualifier: enables
  review:
    summary: Direct kinetic characterization of CPT1A carnitine O-palmitoyltransferase
      activity (KM/Vmax for carnitine and palmitoyl-CoA), with the G710E variant shown
      to be catalytically inactive.
    action: ACCEPT
    reason: Direct experimental support for the core catalytic function of CPT1A.
    supported_by:
    - reference_id: PMID:11350182
      supporting_text: CPT1A is totally inactive
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: PMID:11350182
  qualifier: located_in
  review:
    summary: Direct evidence that CPT1A localizes to the mitochondrion (mitochondrial
      targeting assessed for the G710E variant). Correct but less specific than the
      outer membrane.
    action: KEEP_AS_NON_CORE
    reason: Supports mitochondrial localization; the informative compartment is the
      mitochondrial outer membrane (GO:0005741). Retained as non-core parent.
    supported_by:
    - reference_id: PMID:11350182
      supporting_text: alters neither mitochondrial targeting nor stability of the
        CPT1A
- term:
    id: GO:0005741
    label: mitochondrial outer membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: Sequence-similarity transfer (from rat Cpt1a, P32198) of the mitochondrial
      outer membrane localization, consistent with the human experimental data.
    action: ACCEPT
    reason: Correct, specific compartment concordant with the human EXP/IMP annotations.
    supported_by:
    - reference_id: PMID:16651524
      supporting_text: an outer mitochondrial membrane enzyme
- term:
    id: GO:0009437
    label: carnitine metabolic process
  evidence_type: IDA
  original_reference_id: PMID:11350182
  qualifier: involved_in
  review:
    summary: Direct-assay evidence for CPT1A's role in carnitine metabolism, consistent
      with its use of L-carnitine as the acyl acceptor.
    action: ACCEPT
    reason: Correct process term supported by direct experimental characterization.
    supported_by:
    - reference_id: PMID:11350182
      supporting_text: a rare disorder
- term:
    id: GO:0004095
    label: carnitine O-palmitoyltransferase activity
  evidence_type: TAS
  original_reference_id: PMID:7892212
  qualifier: enables
  review:
    summary: Traceable-author-statement citing characterization of the human liver
      CPT I enzyme (EC 2.3.1.21).
    action: ACCEPT
    reason: Supports the core carnitine O-palmitoyltransferase activity of CPT1A.
    supported_by:
    - reference_id: PMID:7892212
      supporting_text: Human liver mitochondrial carnitine palmitoyltransferase I
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: TAS
  original_reference_id: PMID:7892212
  qualifier: located_in
  review:
    summary: Traceable-author-statement for mitochondrial localization of the human
      liver CPT I. Correct but general.
    action: KEEP_AS_NON_CORE
    reason: Supports mitochondrial localization at low specificity; outer membrane
      is the informative compartment. Retained as non-core parent.
    supported_by:
    - reference_id: PMID:7892212
      supporting_text: Human liver mitochondrial carnitine palmitoyltransferase I
- term:
    id: GO:0006635
    label: fatty acid beta-oxidation
  evidence_type: TAS
  original_reference_id: PMID:7892212
  qualifier: involved_in
  review:
    summary: Traceable-author-statement placing human liver CPT I in mitochondrial
      fatty acid beta-oxidation, where it catalyzes the committed import step.
    action: ACCEPT
    reason: Correct, central process term consistent with CPT1A biology and corroborated
      by IEA/ISS annotations.
    supported_by:
    - reference_id: PMID:7892212
      supporting_text: Human liver mitochondrial carnitine palmitoyltransferase I
core_functions:
- description: Catalyzes the rate-limiting, malonyl-CoA-inhibited transfer of long-chain
    acyl groups from acyl-CoA thioesters to L-carnitine at the mitochondrial outer
    membrane, forming long-chain acylcarnitine and CoA and committing long-chain fatty
    acids to mitochondrial import and beta-oxidation.
  molecular_function:
    id: GO:0004095
    label: carnitine O-palmitoyltransferase activity
  directly_involved_in:
  - id: GO:0006635
    label: fatty acid beta-oxidation
  - id: GO:0006853
    label: carnitine shuttle
  - id: GO:0001676
    label: long-chain fatty acid metabolic process
  locations:
  - id: GO:0005741
    label: mitochondrial outer membrane
  supported_by:
  - reference_id: PMID:14517221
    supporting_text: Carnitine palmitoyltransferase 1A (CPT1A) is the
  - reference_id: PMID:16651524
    supporting_text: controls entry of fatty acids into mitochondria and, thereby,
      fatty acid oxidation
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  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:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:11350182
  title: Molecular and enzymatic characterization of a unique carnitine palmitoyltransferase
    1A mutation in the Hutterite community.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Abstract-only cache; supports CPT1A catalytic activity (G710E variant
      totally inactive), mitochondrial targeting, and CPT1A deficiency as a disorder
      of mitochondrial fatty-acid oxidation. Quotes verified verbatim against the
      cached abstract.
- id: PMID:14517221
  title: Functional and structural basis of carnitine palmitoyltransferase 1A deficiency.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Abstract-only cache; establishes CPT1A as the key regulatory enzyme
      of hepatic long-chain fatty acid beta-oxidation and that G709E/G710E abolish
      activity. Quotes verified verbatim.
- id: PMID:16651524
  title: The brain-specific carnitine palmitoyltransferase-1c regulates energy homeostasis.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Full text available. Primarily about the brain isoform CPT1C but
      explicitly states CPT1a/CPT1b catalyze acyl transfer to carnitine, that CPT1
      is an outer mitochondrial membrane enzyme controlling fatty-acid entry, and
      that malonyl-CoA is an established inhibitor. Used to support CPT1A biology and
      to distinguish CPT1C-specific feeding-behavior roles.
- id: PMID:19946888
  title: Defining the membrane proteome of NK cells.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput NK-cell membrane proteome; supports only a generic
      membrane localization for CPT1A, off-context for its function.
- id: PMID:21492153
  title: Analysis of proteomic changes induced upon cellular differentiation of the
    human intestinal cell line Caco-2.
  findings: []
  reference_review:
    relevance: LOW
    correctness: MISCITED
    review_notes: CPT1A up-regulation is a correlative observation among lipid-metabolism
      proteins during Caco-2 differentiation; does not establish that CPT1A drives
      epithelial cell differentiation (GO:0030855).
- id: PMID:34800366
  title: Quantitative high-confidence human mitochondrial proteome and its dynamics
    in cellular context.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: High-throughput mitochondrial proteome; supports mitochondrial localization
      of CPT1A at low specificity.
- id: PMID:38016475
  title: CPT1A induction following epigenetic perturbation promotes MAVS palmitoylation
    and activation to potentiate antitumor immunity.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Abstract-only cache; establishes the non-catalytic scaffold function
      (CPT1A recruits ER ZDHHC4 to palmitoylate/stabilize MAVS, sustaining the type
      I IFN response). Supports GO:0030674 and GO:0045089. Quotes verified verbatim.
- id: PMID:7892212
  title: 'Human liver mitochondrial carnitine palmitoyltransferase I: characterization
    of its cDNA and chromosomal localization and partial analysis of the gene.'
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Abstract available; original cloning/characterization of human liver
      CPT I (EC 2.3.1.21), distinct from CPT II, on chromosome 11q. Foundational for
      the core catalytic function.
- id: PMID:9691089
  title: Molecular basis of hepatic carnitine palmitoyltransferase I deficiency.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Abstract-only cache; D454G disease variant retains ~2% activity,
      confirming the core carnitine O-palmitoyltransferase activity and CPT1A deficiency
      biology. Quotes verified verbatim.
- id: Reactome:R-HSA-200406
  title: CPT1A transfers PALM to CAR
  findings: []
- id: Reactome:R-HSA-200425
  title: Carnitine shuttle
  findings: []