CPT2

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005739 mitochondrion	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (PAN-GO) inference that CPT2 is active in the mitochondrion. Correct but general; CPT2 is more precisely at the mitochondrial inner membrane (matrix side). Accept as a correct broad localization. Reason: CPT2 is a well-established mitochondrial enzyme. The IBA reflects the conserved mitochondrial localization across the ortholog set and is consistent with all experimental data. Supporting Evidence: PMID:1988962 an inner mitochondrial membrane enzyme that plays a major role in
GO:0004095 carnitine O-palmitoyltransferase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic inference of the core molecular function, carnitine O-palmitoyltransferase (EC 2.3.1.21). This is the defining activity of CPT2 and is directly supported by human enzyme assays. Reason: Well-supported core function; the IBA is at the correct level of specificity and agrees with direct experimental evidence in human CPT2. Supporting Evidence: PMID:20538056 CPT2 is active with medium (C8-C12) and long-chain (C14-C18) acyl-CoA esters
GO:0006635 fatty acid beta-oxidation	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic inference that CPT2 is involved in fatty acid beta-oxidation. By regenerating matrix acyl-CoA, CPT2 is required for long-chain fatty acids to enter beta-oxidation. Core biological process. Reason: The carnitine shuttle step catalyzed by CPT2 is an obligatory prerequisite for mitochondrial long-chain fatty acid beta-oxidation; this is confirmed both by disease phenotypes and enzyme studies. Supporting Evidence: PMID:25578732 Once inside the mitochondrial matrix, CPT2 generates acyl-CoAs from acyl-carnitines to initiate the beta-oxidation of long chain fatty acids to acetyl-CoA
GO:0004095 carnitine O-palmitoyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic (multi-method, includes Rhea RHEA:12661 / EC 2.3.1.21) assignment of carnitine O-palmitoyltransferase activity. Correct core molecular function. Reason: Matches the experimentally verified catalytic activity of human CPT2 (RHEA:12661, EC 2.3.1.21). Supporting Evidence: PMID:20538056 CPT2 is active with medium (C8-C12) and long-chain (C14-C18) acyl-CoA esters
GO:0005743 mitochondrial inner membrane	IEA GO_REF:0000044	ACCEPT	Summary: Subcellular-location mapping (UniProt SL-0168) to mitochondrial inner membrane. Correct; CPT2 is a peripheral inner-membrane protein on the matrix side. Reason: Agrees with the UniProt-curated subcellular location and with the topology features (intramembrane 179-208; matrix-facing catalytic domain). Supporting Evidence: file:human/CPT2/CPT2-uniprot.txt Mitochondrion inner membrane; Peripheral membrane
GO:0008458 carnitine O-octanoyltransferase activity	IEA GO_REF:0000116	ACCEPT	Summary: Rhea-based (RHEA:17177) electronic assignment of carnitine O-octanoyltransferase activity (C8 acyl-CoA). CPT2 is experimentally active toward medium-chain (C8-C12) acyl-CoAs, so this is a genuine, if secondary, activity of the same catalytic site. Reason: Human CPT2 has measurable activity with octanoyl-CoA (medium chain); this reflects the broad chain-length specificity of the single carnitine acyltransferase active site rather than a distinct enzyme, but the activity is real and experimentally documented. Supporting Evidence: PMID:20538056 CPT2 is active with medium (C8-C12) and long-chain (C14-C18) acyl-CoA esters
GO:0015909 long-chain fatty acid transport	IEA GO_REF:0000117	MODIFY	Summary: ARBA machine-learning assignment of long-chain fatty acid transport. CPT2 does not itself transport fatty acids or acylcarnitines across the membrane (that is done by CPT1 plus the carnitine/acylcarnitine translocase SLC25A20); CPT2 is the matrix-side enzyme that regenerates acyl-CoA. The functional essence (enabling mitochondrial long-chain FA import for oxidation) is sound but the transport term mis-describes the mechanism. Reason: CPT2 is an acyltransferase, not a transporter. Its contribution to long-chain fatty acid uptake is indirect (completing the carnitine shuttle). The more accurate terms are the carnitine shuttle and fatty acid beta-oxidation processes it enables. Proposed replacements: carnitine shuttle fatty acid beta-oxidation Supporting Evidence: PMID:25578732 Once inside the mitochondrial matrix, CPT2 generates acyl-CoAs from acyl-carnitines to initiate the beta-oxidation of long chain fatty acids to acetyl-CoA
GO:0016746 acyltransferase activity	IEA GO_REF:0000002	MODIFY	Summary: InterPro2GO (IPR000542, carnitine acyltransferase) mapping to the general parent term acyltransferase activity. Correct but far too general given that the specific carnitine O-palmitoyltransferase activity (GO:0004095) is directly established for CPT2. Reason: An uninformative high-level term; the specific molecular function is known and experimentally supported. Proposed replacements: carnitine O-palmitoyltransferase activity Supporting Evidence: PMID:20538056 CPT2 is active with medium (C8-C12) and long-chain (C14-C18) acyl-CoA esters
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	MARK AS OVER ANNOTATED	Summary: High-throughput affinity-capture (BioPlex) interactome screen. Bare protein binding is uninformative and does not describe a specific molecular function of CPT2. CPT2 appears only in the large-scale interaction dataset. Reason: Per curation guidelines, bare GO:0005515 protein binding from high-throughput interactome data adds no functional information and should not be treated as a core or informative annotation. Retained (not removed) as it derives from experimental IPI evidence. Supporting Evidence: PMID:28514442 Architecture of the human interactome defines protein communities and disease networks.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Binary yeast two-hybrid interactome (HuRI); partners recorded in UniProt include CYSRT1 (A8MQ03) and OTX1 (P32242). Bare protein binding is uninformative about CPT2 molecular function. Reason: Bare protein binding from a high-throughput binary interactome screen does not describe a specific, biologically meaningful molecular function of CPT2. Retained as experimental IPI evidence rather than removed. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: Cell-specific proteome-scale interactome (BioPlex, HCT116/293T); interaction with MCUR1 (Q96AQ8) recorded. Bare protein binding is uninformative. Reason: As with the other interactome-derived protein binding annotations, this adds no specific functional information for CPT2. Retained as experimental IPI evidence. Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
GO:0005759 mitochondrial matrix	IEA GO_REF:0000107	ACCEPT	Summary: Ortholog-transfer (Ensembl Compara, from mouse P52825) assignment placing the active enzyme on the matrix side. Consistent with the UniProt topology (matrix-facing catalytic domain, matrix side of the inner membrane). Reason: CPT2's catalytic domain faces the mitochondrial matrix; is_active_in mitochondrial matrix accurately reflects where catalysis occurs, complementing the inner-membrane location. Supporting Evidence: file:human/CPT2/CPT2-uniprot.txt Mitochondrion inner membrane; Peripheral membrane
GO:0006853 carnitine shuttle	IEA GO_REF:0000107	ACCEPT	Summary: Ortholog-transfer assignment of the carnitine shuttle process. CPT2 catalyzes the final matrix-side step of the shuttle, regenerating acyl-CoA. Core biological process. Reason: CPT2 is a defining member of the carnitine shuttle; this is the process most specifically describing its physiological role. Supporting Evidence: file:human/CPT2/CPT2-uniprot.txt Reconverts
GO:0120162 positive regulation of cold-induced thermogenesis	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ortholog-transfer (from mouse) of a role in positive regulation of cold-induced thermogenesis. Based on adipose-specific Cpt2 knockout mice that become hypothermic after cold challenge and fail to upregulate thermogenic genes in brown adipose tissue. This is a genuine but tissue-specific (BAT), downstream organismal consequence of CPT2-dependent fatty acid oxidation, not the core enzymatic function. Reason: The phenotype is real (mouse adipose Cpt2 loss impairs cold-induced thermogenesis) but it is a context-dependent physiological role in a specific tissue, downstream of the enzyme's fatty acid beta-oxidation function. Keep as non-core. Supporting Evidence: PMID:25578732 CPT2(A-/-) mice became hypothermic after an PMID:25578732 adipose tissue fatty acid oxidation is not only required for acute cold adaptation, but also for the induction of thermogenic genes in BAT
GO:0006853 carnitine shuttle	TAS Reactome:R-HSA-200425	ACCEPT	Summary: Reactome (Carnitine shuttle pathway) traceable-author-statement assignment. CPT2 catalyzes the matrix-side acylcarnitine-to-acyl-CoA step of this pathway. Core process, correctly attributed. Reason: Directly and authoritatively describes CPT2's role in the carnitine shuttle. Supporting Evidence: file:human/CPT2/CPT2-uniprot.txt Reconverts
GO:0006635 fatty acid beta-oxidation	IEA GO_REF:0000041	ACCEPT	Summary: UniPathway (UPA00659, fatty acid beta-oxidation) mapping. CPT2 is required for long-chain fatty acids to enter beta-oxidation. Core process. Reason: Consistent with the curated UniProt PATHWAY assignment (fatty acid beta-oxidation) and with all experimental data. Supporting Evidence: PMID:25578732 Once inside the mitochondrial matrix, CPT2 generates acyl-CoAs from acyl-carnitines to initiate the beta-oxidation of long chain fatty acids to acetyl-CoA
GO:0005739 mitochondrion	IDA GO_REF:0000052	ACCEPT	Summary: Direct immunofluorescence (Human Protein Atlas) localization to the mitochondrion. Correct, though more precisely the inner membrane / matrix. Reason: Direct experimental localization consistent with all other evidence. Broad but correct. Supporting Evidence: PMID:1988962 an inner mitochondrial membrane enzyme that plays a major role in
GO:0016406 carnitine O-acyltransferase activity	EXP PMID:20538056 Carnitine palmitoyltransferase 2: New insights on the substr...	ACCEPT	Summary: Experimental (substrate profiling of human CPT2) support for carnitine O-acyltransferase activity, the parent term covering both the palmitoyl (C16) and octanoyl (C8) activities. Accurate. Reason: Directly supported by enzyme assays showing CPT2 acts on medium- and long-chain acyl-CoAs. Correct, if somewhat general relative to the more specific GO:0004095. Supporting Evidence: PMID:20538056 CPT2 is active with medium (C8-C12) and long-chain (C14-C18) acyl-CoA esters
GO:0016406 carnitine O-acyltransferase activity	EXP PMID:7711730 Carnitine palmitoyltransferase II deficiency: structure of t...	ACCEPT	Summary: Experimental support (transfection/COS-cell CPT II activity assays in the context of disease-mutation characterization) for carnitine O-acyltransferase activity of CPT2. Accurate parent-level MF. Reason: The study measured CPT II catalytic activity in cells expressing wild-type and mutant CPT2, confirming carnitine acyltransferase activity for the gene product. Supporting Evidence: PMID:7711730 Transfection experiments in COS cells demonstrated that both mutations drastically depressed the catalytic activity of CPT II.
GO:0004095 carnitine O-palmitoyltransferase activity	EXP PMID:24780397 Functional analysis of iPSC-derived myocytes from a patient ...	ACCEPT	Summary: Experimental support (CPT II-deficient patient iPSC-derived myocytes; accumulation of C16 palmitoylcarnitine reflecting loss of the palmitoyltransferase step) for carnitine O-palmitoyltransferase activity. Core molecular function. Reason: The disease-model data (C16 acylcarnitine accumulation with impaired CPT2) confirm the carnitine O-palmitoyltransferase activity of human CPT2. Supporting Evidence: PMID:24780397 CPT II-deficient myocytes accumulated more palmitoylcarnitine (C16)
GO:0008458 carnitine O-octanoyltransferase activity	EXP PMID:20538056 Carnitine palmitoyltransferase 2: New insights on the substr...	ACCEPT	Summary: Experimental support for octanoyl-CoA (C8, medium chain) activity of human CPT2 from the substrate-specificity study. Genuine secondary activity of the same catalytic site. Reason: Human CPT2 has measurable medium-chain (C8) carnitine acyltransferase activity; experimentally documented. Supporting Evidence: PMID:20538056 CPT2 is active with medium (C8-C12) and long-chain (C14-C18) acyl-CoA esters
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	ACCEPT	Summary: High-throughput proteomic identification of CPT2 in the high-confidence human mitochondrial proteome (MitoCoP). Confirms mitochondrial localization. Reason: Consistent with all other localization evidence; a correct, if broad, mitochondrial assignment from a rigorous proteomic dataset. Supporting Evidence: PMID:34800366 mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP)
GO:0001676 long-chain fatty acid metabolic process	IDA PMID:20538056 Carnitine palmitoyltransferase 2: New insights on the substr...	ACCEPT	Summary: Direct experimental support that CPT2 participates in long-chain fatty acid metabolism, from its activity toward long-chain (C14-C18) acyl-CoAs. Accurate process annotation. Reason: CPT2's substrate profile and its obligatory role in mitochondrial long-chain fatty acid oxidation directly support this process. Supporting Evidence: PMID:20538056 CPT2 is active with medium (C8-C12) and long-chain (C14-C18) acyl-CoA esters
GO:0004095 carnitine O-palmitoyltransferase activity	IDA PMID:20538056 Carnitine palmitoyltransferase 2: New insights on the substr...	ACCEPT	Summary: Direct enzyme assay (human CPT2 expressed in yeast) of carnitine O-palmitoyltransferase activity toward long-chain acyl-CoAs. This is the primary experimental basis for the core molecular function. Reason: Strongest, most specific experimental support for the defining catalytic activity of CPT2. Supporting Evidence: PMID:20538056 CPT2 is active with medium (C8-C12) and long-chain (C14-C18) acyl-CoA esters
GO:0006635 fatty acid beta-oxidation	IDA PMID:20538056 Carnitine palmitoyltransferase 2: New insights on the substr...	ACCEPT	Summary: Direct experimental support that CPT2 functions in fatty acid beta-oxidation, based on demonstration that CPT2 handles the medium/long-chain acyl-CoAs that feed beta-oxidation. Core process. Reason: CPT2's role in regenerating matrix acyl-CoA is an obligatory step enabling beta-oxidation, directly supported by its substrate specificity and by disease phenotypes. Supporting Evidence: PMID:20538056 reflect the potentially toxic
GO:0009437 carnitine metabolic process	IDA PMID:20538056 Carnitine palmitoyltransferase 2: New insights on the substr...	ACCEPT	Summary: Direct experimental support that CPT2 participates in carnitine metabolism, as it interconverts acylcarnitine and free carnitine during the shuttle. Accurate. Reason: CPT2 consumes acylcarnitine and releases free L-carnitine, directly acting on carnitine-containing metabolites; supported by the substrate/product profiling. Supporting Evidence: PMID:20538056 CPT2 is able to reverse its physiological mechanism for
GO:0016746 acyltransferase activity	IDA PMID:20538056 Carnitine palmitoyltransferase 2: New insights on the substr...	MODIFY	Summary: Direct experimental support at the general acyltransferase level. As with the InterPro IEA, this parent term is correct but far less informative than the specific carnitine O-palmitoyltransferase activity established in the same study. Reason: Too general; the specific molecular function (carnitine O-palmitoyltransferase) is directly demonstrated in this very paper and should be used instead. Proposed replacements: carnitine O-palmitoyltransferase activity Supporting Evidence: PMID:20538056 CPT2 is active with medium (C8-C12) and long-chain (C14-C18) acyl-CoA esters
GO:0120162 positive regulation of cold-induced thermogenesis	ISS PMID:25578732 Adipose fatty acid oxidation is required for thermogenesis a...	KEEP AS NON CORE	Summary: Sequence/ortholog-based (ISS from mouse P52825) transfer of a role in positive regulation of cold-induced thermogenesis, grounded in adipose-specific Cpt2 knockout mice that become hypothermic and fail to induce BAT thermogenic genes. Genuine but tissue-specific downstream physiological role. Reason: Real phenotype in mouse adipose tissue, but a context-dependent organismal consequence downstream of CPT2's fatty acid beta-oxidation function rather than its core molecular activity. Keep as non-core. Supporting Evidence: PMID:25578732 CPT2(A-/-) mice became hypothermic after an PMID:25578732 adipose tissue fatty acid oxidation is not only required for acute cold adaptation, but also for the induction of thermogenic genes in BAT
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-1989773	ACCEPT	Summary: Reactome traceable-author-statement localization to the mitochondrial inner membrane. Correct; CPT2 is a peripheral inner-membrane protein on the matrix side. Reason: Matches the curated UniProt subcellular location and topology. Supporting Evidence: file:human/CPT2/CPT2-uniprot.txt Mitochondrion inner membrane; Peripheral membrane
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-200410	ACCEPT	Summary: Reactome (CPT2 converts acylcarnitine to acyl-CoA) traceable-author-statement localization to the mitochondrial inner membrane. Correct core localization. Reason: Matches curated UniProt localization; this Reactome reaction is exactly the matrix-side step CPT2 catalyzes. Supporting Evidence: file:human/CPT2/CPT2-uniprot.txt Mitochondrion inner membrane; Peripheral membrane
GO:0004095 carnitine O-palmitoyltransferase activity	NAS PMID:1988962 cDNA cloning, sequence analysis, and chromosomal localizatio...	ACCEPT	Summary: Non-traceable author statement (original cloning paper describing CPT2 as palmitoyl-CoA:L-carnitine O-palmitoyltransferase, EC 2.3.1.21). Correct core molecular function, later confirmed experimentally. Reason: The defining catalytic activity of CPT2, asserted in the founding cloning study and subsequently verified by direct assay. Supporting Evidence: PMID:1988962 an inner mitochondrial membrane enzyme that plays a major role in
GO:0005743 mitochondrial inner membrane	NAS PMID:1988962 cDNA cloning, sequence analysis, and chromosomal localizatio...	ACCEPT	Summary: Non-traceable author statement from the cloning paper describing CPT2 as an inner mitochondrial membrane enzyme. Correct core localization. Reason: Consistent with curated UniProt subcellular location and with experimental proteomic/imaging localization. Supporting Evidence: PMID:1988962 an inner mitochondrial membrane enzyme that plays a major role in

Gene Description

Existing Annotations Review

Core Functions

Participation in mitochondrial long-chain fatty acid beta-oxidation by regenerating the matrix acyl-CoA pool, an obligatory step that allows imported long-chain fatty acids to be oxidized to acetyl-CoA.

References

Deep Research

Falcon

📚 Additional Documentation

Notes

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