Carnitine O-palmitoyltransferase 1, liver isoform (CPT1A, L-CPT1) is a polytopic integral protein of the mitochondrial outer membrane, with two transmembrane segments, cytosolic N- and C-terminal domains and a short intermembrane-space loop. Its C-terminal catalytic domain, a member of the carnitine/choline acetyltransferase family with catalytic His473 and Asp477, transfers long-chain acyl groups from acyl-CoA to L-carnitine to form acylcarnitines. This is the first step of the carnitine shuttle and the rate-limiting, regulated entry point of long-chain fatty acids into mitochondrial beta-oxidation. Activity is inhibited by malonyl-CoA, the first intermediate of fatty acid synthesis, linking oxidation to lipogenic state; sensitivity is tuned by the N-terminal regulatory segment (a membrane-curvature-responsive structural switch), the loop/TM2 region, CK2 phosphorylation and membrane lipid environment. CPT1A forms trimers/hexamers through TM2 and associates with ACSL1 and VDAC in the outer membrane. Expressed mainly in liver and kidney, it controls hepatic fatty acid oxidation, ketogenesis and triglyceride output, and its expression is strongly induced by fasting, fatty acids and PPARalpha agonists. The human ortholog additionally has reported lysine succinyltransferase activity and a role recruiting ZDHHC4 to MAVS in type I interferon signalling.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001666 response to hypoxia | IEP PMID:33310031 WY14643 improves left ventricular myocardial mitochondrial a... | KEEP AS NON CORE | Summary: Cpt1a expression changes in hypoxic/obese rat myocardium. Reason: Expression-pattern (IEP) annotation: the study reports that Cpt1a mRNA/protein/activity changes under this condition. This is a genuine but peripheral observation about regulation of Cpt1a expression (largely via PPARalpha) rather than a function of the protein; kept as non-core. Supporting Evidence: PMID:33310031 WY14643 upregulated PPARα, PGC1α, and CPT1α, and downregulated ACC2. file:rat/Cpt1a/Cpt1a-deep-research-manual.md expression responses, not functions. |
| GO:0001676 long-chain fatty acid metabolic process | IDA PMID:21990363 An environment-dependent structural switch underlies the reg... | ACCEPT | Summary: CPT1A participates in long-chain fatty acid metabolic process by forming long-chain acylcarnitines. Reason: CPT1A converts long-chain acyl-CoAs to acylcarnitines, a defining step of long-chain fatty acid metabolism; GO:0001676 is the appropriate process level and is consistent with the long-chain substrate specificity. Supporting Evidence: PMID:21990363 The enzyme carnitine palmitoyltransferase 1 (CPT1), which is anchored in the outer mitochondrial membrane (OMM), controls the rate-limiting step in fatty acid β-oxidation in mammalian tissues. file:rat/Cpt1a/Cpt1a-uniprot.txt Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion |
| GO:0001676 long-chain fatty acid metabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: CPT1A participates in long-chain fatty acid metabolic process by forming long-chain acylcarnitines. Reason: CPT1A converts long-chain acyl-CoAs to acylcarnitines, a defining step of long-chain fatty acid metabolism; GO:0001676 is the appropriate process level and is consistent with the long-chain substrate specificity. Ensembl Compara transfer from human CPT1A, consistent with rat experimental evidence. Supporting Evidence: file:rat/Cpt1a/Cpt1a-uniprot.txt Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion PMID:18349115 Overexpression of CPT-1a increased the rate of beta-oxidation and ketogenesis by approximately 70% |
| GO:0001676 long-chain fatty acid metabolic process | IMP PMID:19302064 Modulation of the hepatic malonyl-CoA-carnitine palmitoyltra... | ACCEPT | Summary: CPT1A participates in long-chain fatty acid metabolic process by forming long-chain acylcarnitines. Reason: CPT1A converts long-chain acyl-CoAs to acylcarnitines, a defining step of long-chain fatty acid metabolism; GO:0001676 is the appropriate process level and is consistent with the long-chain substrate specificity. Supporting Evidence: PMID:19302064 counteracted the inhibition of oleate beta-oxidation induced by 20 mM glucose/10 nM insulin file:rat/Cpt1a/Cpt1a-uniprot.txt Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion |
| GO:0001676 long-chain fatty acid metabolic process | ISO GO_REF:0000121 | ACCEPT | Summary: CPT1A participates in long-chain fatty acid metabolic process by forming long-chain acylcarnitines. Reason: CPT1A converts long-chain acyl-CoAs to acylcarnitines, a defining step of long-chain fatty acid metabolism; GO:0001676 is the appropriate process level and is consistent with the long-chain substrate specificity. ISO transfer from human CPT1A, consistent with rat experimental evidence. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P50416 · CPT1A (human) SUPPORTS TRANSFER Human CPT1A is the 1:1 ortholog with the same activity; rat has direct evidence. Supporting Evidence: file:rat/Cpt1a/Cpt1a-uniprot.txt Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion PMID:18349115 Overexpression of CPT-1a increased the rate of beta-oxidation and ketogenesis by approximately 70% |
| GO:0001676 long-chain fatty acid metabolic process | TAS PMID:9461513 Cloning and characterization of the promoter for the liver i... | ACCEPT | Summary: CPT1A participates in long-chain fatty acid metabolic process by forming long-chain acylcarnitines. Reason: CPT1A converts long-chain acyl-CoAs to acylcarnitines, a defining step of long-chain fatty acid metabolism; GO:0001676 is the appropriate process level and is consistent with the long-chain substrate specificity. Supporting Evidence: file:rat/Cpt1a/Cpt1a-uniprot.txt Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion PMID:9461513 Carnitine palmitoyltransferase I (CPTI) catalyses the transfer of long chain fatty acids to carnitine for translocation across the mitochondrial inner membrane. |
| GO:0004095 carnitine O-palmitoyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Carnitine O-palmitoyltransferase activity is the defining catalytic activity of CPT1A. Reason: Rat liver CPT1A has been expressed and assayed in yeast, COS7 and hepatocytes and in isolated mitochondrial outer membranes, with kinetic parameters and catalytic-residue mutagenesis (His473, Asp477). This is the core MF. IBA from PTHR22589 node PTN001097100, which covers the CPT1 clade; rat Cpt1a sits within it and has its own experimental annotations among the descendant evidence, which is expected, not circular. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001097100 · PANTHER:PTN001097100 SUPPORTS TRANSFER Node seeded by experimentally characterised CPT1A/CPT1B from human, mouse and rat; target retains catalytic His473/Asp477. Supporting Evidence: file:rat/Cpt1a/Cpt1a-uniprot.txt Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion PMID:24222496 The enzyme carnitine palmitoyltransferase 1 (CPT1) catalyzes the transfer of an acyl group from acyl-CoA to carnitine to form acylcarnitine PMID:14711372 We conclude that the catalytic residues are His473 and Asp477, while Ser687 probably stabilizes the transition state. |
| GO:0004095 carnitine O-palmitoyltransferase activity | IDA PMID:11790778 Pig liver carnitine palmitoyltransferase. Chimera studies sh... | ACCEPT | Summary: Carnitine O-palmitoyltransferase activity is the defining catalytic activity of CPT1A. Reason: Rat liver CPT1A has been expressed and assayed in yeast, COS7 and hepatocytes and in isolated mitochondrial outer membranes, with kinetic parameters and catalytic-residue mutagenesis (His473, Asp477). This is the core MF. Supporting Evidence: PMID:11790778 Pig and rat liver carnitine palmitoyltransferase I (L-CPTI) share common K(m) values for palmitoyl-CoA and carnitine. |
| GO:0004095 carnitine O-palmitoyltransferase activity | IDA PMID:11988095 Adenovirus-mediated overexpression of liver carnitine palmit... | ACCEPT | Summary: Carnitine O-palmitoyltransferase activity is the defining catalytic activity of CPT1A. Reason: Rat liver CPT1A has been expressed and assayed in yeast, COS7 and hepatocytes and in isolated mitochondrial outer membranes, with kinetic parameters and catalytic-residue mutagenesis (His473, Asp477). This is the core MF. Supporting Evidence: PMID:11988095 a 6-fold increase in the CPT activity, and an increase in fatty acid oxidation |
| GO:0004095 carnitine O-palmitoyltransferase activity | IDA PMID:12499375 Identification of conserved amino acid residues in rat liver... | ACCEPT | Summary: Carnitine O-palmitoyltransferase activity is the defining catalytic activity of CPT1A. Reason: Rat liver CPT1A has been expressed and assayed in yeast, COS7 and hepatocytes and in isolated mitochondrial outer membranes, with kinetic parameters and catalytic-residue mutagenesis (His473, Asp477). This is the core MF. Supporting Evidence: PMID:12499375 The catalytic efficiency (V(max)/K(m)) of CPT I in mutants A478G and C608A and all Met(593) mutants toward carnitine as substrate was clearly increased. |
| GO:0004095 carnitine O-palmitoyltransferase activity | IDA PMID:12540837 Identification by mutagenesis of conserved arginine and glut... | ACCEPT | Summary: Carnitine O-palmitoyltransferase activity is the defining catalytic activity of CPT1A. Reason: Rat liver CPT1A has been expressed and assayed in yeast, COS7 and hepatocytes and in isolated mitochondrial outer membranes, with kinetic parameters and catalytic-residue mutagenesis (His473, Asp477). This is the core MF. Supporting Evidence: PMID:12540837 Substitution of Glu-603 with alanine or histidine resulted in complete loss of L-CPTI activity. |
| GO:0004095 carnitine O-palmitoyltransferase activity | IDA PMID:12826662 A single amino acid change (substitution of the conserved Gl... | ACCEPT | Summary: Carnitine O-palmitoyltransferase activity is the defining catalytic activity of CPT1A. Reason: Rat liver CPT1A has been expressed and assayed in yeast, COS7 and hepatocytes and in isolated mitochondrial outer membranes, with kinetic parameters and catalytic-residue mutagenesis (His473, Asp477). This is the core MF. Supporting Evidence: PMID:12826662 Carnitine palmitoyltransferase I (CPTI) catalyzes the conversion of long-chain fatty acyl-CoAs to acylcarnitines in the presence of l-carnitine. |
| GO:0004095 carnitine O-palmitoyltransferase activity | IDA PMID:14711372 Structural model of carnitine palmitoyltransferase I based o... | ACCEPT | Summary: Carnitine O-palmitoyltransferase activity is the defining catalytic activity of CPT1A. Reason: Rat liver CPT1A has been expressed and assayed in yeast, COS7 and hepatocytes and in isolated mitochondrial outer membranes, with kinetic parameters and catalytic-residue mutagenesis (His473, Asp477). This is the core MF. Supporting Evidence: PMID:14711372 We conclude that the catalytic residues are His473 and Asp477, while Ser687 probably stabilizes the transition state. |
| GO:0004095 carnitine O-palmitoyltransferase activity | IDA PMID:15247243 Phosphorylation of rat liver mitochondrial carnitine palmito... | ACCEPT | Summary: Carnitine O-palmitoyltransferase activity is the defining catalytic activity of CPT1A. Reason: Rat liver CPT1A has been expressed and assayed in yeast, COS7 and hepatocytes and in isolated mitochondrial outer membranes, with kinetic parameters and catalytic-residue mutagenesis (His473, Asp477). This is the core MF. Supporting Evidence: PMID:15247243 led to increased catalytic activity and rendered malonyl-CoA inhibition of CPT-I from competitive to uncompetitive |
| GO:0004095 carnitine O-palmitoyltransferase activity | IDA PMID:18349115 A moderate increase in carnitine palmitoyltransferase 1a act... | ACCEPT | Summary: Carnitine O-palmitoyltransferase activity is the defining catalytic activity of CPT1A. Reason: Rat liver CPT1A has been expressed and assayed in yeast, COS7 and hepatocytes and in isolated mitochondrial outer membranes, with kinetic parameters and catalytic-residue mutagenesis (His473, Asp477). This is the core MF. Supporting Evidence: PMID:18349115 Overexpression of CPT-1a increased the rate of beta-oxidation and ketogenesis by approximately 70% |
| GO:0004095 carnitine O-palmitoyltransferase activity | IDA PMID:21990363 An environment-dependent structural switch underlies the reg... | ACCEPT | Summary: Carnitine O-palmitoyltransferase activity is the defining catalytic activity of CPT1A. Reason: Rat liver CPT1A has been expressed and assayed in yeast, COS7 and hepatocytes and in isolated mitochondrial outer membranes, with kinetic parameters and catalytic-residue mutagenesis (His473, Asp477). This is the core MF. Supporting Evidence: file:rat/Cpt1a/Cpt1a-uniprot.txt Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion |
| GO:0004095 carnitine O-palmitoyltransferase activity | IDA PMID:24222496 Comparison of the catalytic activities of three isozymes of ... | ACCEPT | Summary: Carnitine O-palmitoyltransferase activity is the defining catalytic activity of CPT1A. Reason: Rat liver CPT1A has been expressed and assayed in yeast, COS7 and hepatocytes and in isolated mitochondrial outer membranes, with kinetic parameters and catalytic-residue mutagenesis (His473, Asp477). This is the core MF. Supporting Evidence: PMID:24222496 The enzyme carnitine palmitoyltransferase 1 (CPT1) catalyzes the transfer of an acyl group from acyl-CoA to carnitine to form acylcarnitine |
| GO:0004095 carnitine O-palmitoyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Carnitine O-palmitoyltransferase activity is the defining catalytic activity of CPT1A. Reason: Rat liver CPT1A has been expressed and assayed in yeast, COS7 and hepatocytes and in isolated mitochondrial outer membranes, with kinetic parameters and catalytic-residue mutagenesis (His473, Asp477). This is the core MF. Combined IEA (ARBA, Ensembl Compara, Rhea/EC) consistent with the experimental data. Supporting Evidence: file:rat/Cpt1a/Cpt1a-uniprot.txt Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion file:rat/Cpt1a/Cpt1a-uniprot.txt Belongs to the carnitine/choline acetyltransferase family |
| GO:0004095 carnitine O-palmitoyltransferase activity | IMP PMID:16908527 The mitochondrial intermembrane loop region of rat carnitine... | ACCEPT | Summary: Carnitine O-palmitoyltransferase activity is the defining catalytic activity of CPT1A. Reason: Rat liver CPT1A has been expressed and assayed in yeast, COS7 and hepatocytes and in isolated mitochondrial outer membranes, with kinetic parameters and catalytic-residue mutagenesis (His473, Asp477). This is the core MF. Mutant/chimera constructs (loop/TM2) were assayed for activity and malonyl-CoA sensitivity. Supporting Evidence: PMID:16908527 Carnitine palmitoyltransferase (CPT) 1A adopts a polytopic conformation within the mitochondrial outer membrane file:rat/Cpt1a/Cpt1a-uniprot.txt Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion |
| GO:0004095 carnitine O-palmitoyltransferase activity | IMP PMID:9169604 Topology of carnitine palmitoyltransferase I in the mitochon... | ACCEPT | Summary: Carnitine O-palmitoyltransferase activity is the defining catalytic activity of CPT1A. Reason: Rat liver CPT1A has been expressed and assayed in yeast, COS7 and hepatocytes and in isolated mitochondrial outer membranes, with kinetic parameters and catalytic-residue mutagenesis (His473, Asp477). This is the core MF. The topology study used activity assays of the native enzyme in intact and outer-membrane-ruptured mitochondria (abstract-only cache); deferring to the curator. Supporting Evidence: PMID:9169604 CPT I adopts a bitopic topology within the mitochondrial outer membrane |
| GO:0004095 carnitine O-palmitoyltransferase activity | ISO GO_REF:0000121 | ACCEPT | Summary: Carnitine O-palmitoyltransferase activity is the defining catalytic activity of CPT1A. Reason: Rat liver CPT1A has been expressed and assayed in yeast, COS7 and hepatocytes and in isolated mitochondrial outer membranes, with kinetic parameters and catalytic-residue mutagenesis (His473, Asp477). This is the core MF. Propagation Review Root cause: NO FAILURE CORE Sources checked: MGI:MGI:1098296 · Cpt1a (mouse) SUPPORTS TRANSFER Mouse ortholog; same activity. Supporting Evidence: file:rat/Cpt1a/Cpt1a-uniprot.txt Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion PMID:24222496 The enzyme carnitine palmitoyltransferase 1 (CPT1) catalyzes the transfer of an acyl group from acyl-CoA to carnitine to form acylcarnitine PMID:14711372 We conclude that the catalytic residues are His473 and Asp477, while Ser687 probably stabilizes the transition state. |
| GO:0004095 carnitine O-palmitoyltransferase activity | ISO GO_REF:0000121 | ACCEPT | Summary: Carnitine O-palmitoyltransferase activity is the defining catalytic activity of CPT1A. Reason: Rat liver CPT1A has been expressed and assayed in yeast, COS7 and hepatocytes and in isolated mitochondrial outer membranes, with kinetic parameters and catalytic-residue mutagenesis (His473, Asp477). This is the core MF. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P50416 · CPT1A (human) SUPPORTS TRANSFER Orthologous CPT1A with the same experimentally established activity. Supporting Evidence: file:rat/Cpt1a/Cpt1a-uniprot.txt Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion PMID:24222496 The enzyme carnitine palmitoyltransferase 1 (CPT1) catalyzes the transfer of an acyl group from acyl-CoA to carnitine to form acylcarnitine PMID:14711372 We conclude that the catalytic residues are His473 and Asp477, while Ser687 probably stabilizes the transition state. |
| GO:0004095 carnitine O-palmitoyltransferase activity | TAS PMID:9461513 Cloning and characterization of the promoter for the liver i... | ACCEPT | Summary: Carnitine O-palmitoyltransferase activity is the defining catalytic activity of CPT1A. Reason: Rat liver CPT1A has been expressed and assayed in yeast, COS7 and hepatocytes and in isolated mitochondrial outer membranes, with kinetic parameters and catalytic-residue mutagenesis (His473, Asp477). This is the core MF. Supporting Evidence: PMID:9461513 Carnitine palmitoyltransferase I (CPTI) catalyses the transfer of long chain fatty acids to carnitine for translocation across the mitochondrial inner membrane. |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: CPT1A is a mitochondrial protein (outer membrane). Reason: Root organelle term (ORGANELLES policy): kept, not refined. Checked the basis: CPT1A is an integral mitochondrial outer membrane protein (topology, import and outer-membrane fractionation studies), so the mitochondrion claim holds; the sub-compartment is carried separately by the GO:0005741 rows. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001097100 · PANTHER:PTN001097100 SUPPORTS TRANSFER Mitochondrial location is conserved across the CPT1 clade (CPT1A/CPT1B); CPT1C (ER) is a separate lineage. Supporting Evidence: file:rat/Cpt1a/Cpt1a-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion outer membrane PMID:9169604 CPT I adopts a bitopic topology within the mitochondrial outer membrane |
| GO:0005739 mitochondrion | IEA GO_REF:0000107 | ACCEPT | Summary: CPT1A is a mitochondrial protein (outer membrane). Reason: Root organelle term (ORGANELLES policy): kept, not refined. Checked the basis: CPT1A is an integral mitochondrial outer membrane protein (topology, import and outer-membrane fractionation studies), so the mitochondrion claim holds; the sub-compartment is carried separately by the GO:0005741 rows. Supporting Evidence: file:rat/Cpt1a/Cpt1a-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion outer membrane PMID:9169604 CPT I adopts a bitopic topology within the mitochondrial outer membrane |
| GO:0005739 mitochondrion | ISO GO_REF:0000121 | ACCEPT | Summary: CPT1A is a mitochondrial protein (outer membrane). Reason: Root organelle term (ORGANELLES policy): kept, not refined. Checked the basis: CPT1A is an integral mitochondrial outer membrane protein (topology, import and outer-membrane fractionation studies), so the mitochondrion claim holds; the sub-compartment is carried separately by the GO:0005741 rows. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P50416 · CPT1A (human) SUPPORTS TRANSFER Human CPT1A is mitochondrial (outer membrane). Supporting Evidence: file:rat/Cpt1a/Cpt1a-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion outer membrane PMID:9169604 CPT I adopts a bitopic topology within the mitochondrial outer membrane |
| GO:0005741 mitochondrial outer membrane | EXP PMID:18192268 CPT1c is localized in endoplasmic reticulum of neurons and h... | ACCEPT | Summary: CPT1A is located in the mitochondrial outer membrane. Reason: CPT1A is a polytopic mitochondrial outer membrane protein with two TM segments, cytosolic N- and C-termini and an intermembrane-space loop; this is where its catalytic activity is exercised. This paper is about CPT1c, but rat CPT1a was used as the mitochondrial comparator (UniProt cites it for location); abstract-only, deferring to curator. Supporting Evidence: file:rat/Cpt1a/Cpt1a-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion outer membrane |
| GO:0005741 mitochondrial outer membrane | EXP PMID:19136561 Self-association of transmembrane domain 2 (TM2), but not TM... | ACCEPT | Summary: CPT1A is located in the mitochondrial outer membrane. Reason: CPT1A is a polytopic mitochondrial outer membrane protein with two TM segments, cytosolic N- and C-termini and an intermembrane-space loop; this is where its catalytic activity is exercised. Supporting Evidence: PMID:19136561 The data indicate that in liver mitochondria in vivo CPT1A exists as a hexamer |
| GO:0005741 mitochondrial outer membrane | IDA PMID:11087756 The N-terminal domain of rat liver carnitine palmitoyltransf... | ACCEPT | Summary: CPT1A is located in the mitochondrial outer membrane. Reason: CPT1A is a polytopic mitochondrial outer membrane protein with two TM segments, cytosolic N- and C-termini and an intermembrane-space loop; this is where its catalytic activity is exercised. Supporting Evidence: PMID:11087756 specify both mitochondrial targeting and anchorage at the outer mitochondrial membrane (OMM) |
| GO:0005741 mitochondrial outer membrane | IDA PMID:15247243 Phosphorylation of rat liver mitochondrial carnitine palmito... | ACCEPT | Summary: CPT1A is located in the mitochondrial outer membrane. Reason: CPT1A is a polytopic mitochondrial outer membrane protein with two TM segments, cytosolic N- and C-termini and an intermembrane-space loop; this is where its catalytic activity is exercised. Supporting Evidence: PMID:15247243 Hepatic carnitine palmitoyltransferase-I (CPT-IL) isolated from mitochondrial outer membranes |
| GO:0005741 mitochondrial outer membrane | IDA PMID:16908527 The mitochondrial intermembrane loop region of rat carnitine... | ACCEPT | Summary: CPT1A is located in the mitochondrial outer membrane. Reason: CPT1A is a polytopic mitochondrial outer membrane protein with two TM segments, cytosolic N- and C-termini and an intermembrane-space loop; this is where its catalytic activity is exercised. Supporting Evidence: PMID:16908527 Carnitine palmitoyltransferase (CPT) 1A adopts a polytopic conformation within the mitochondrial outer membrane |
| GO:0005741 mitochondrial outer membrane | IDA PMID:21622568 Mitochondrial carnitine palmitoyltransferase 1a (CPT1a) is p... | ACCEPT | Summary: CPT1A is located in the mitochondrial outer membrane. Reason: CPT1A is a polytopic mitochondrial outer membrane protein with two TM segments, cytosolic N- and C-termini and an intermembrane-space loop; this is where its catalytic activity is exercised. Supporting Evidence: PMID:21622568 CPT1a (carnitine palmitoyltransferase 1a) in the liver mitochondrial outer membrane (MOM) catalyzes the primary regulated step in overall mitochondrial fatty acid oxidation. |
| GO:0005741 mitochondrial outer membrane | IDA PMID:9169604 Topology of carnitine palmitoyltransferase I in the mitochon... | ACCEPT | Summary: CPT1A is located in the mitochondrial outer membrane. Reason: CPT1A is a polytopic mitochondrial outer membrane protein with two TM segments, cytosolic N- and C-termini and an intermembrane-space loop; this is where its catalytic activity is exercised. Supporting Evidence: PMID:9169604 CPT I adopts a bitopic topology within the mitochondrial outer membrane |
| GO:0005741 mitochondrial outer membrane | IEA GO_REF:0000120 | ACCEPT | Summary: CPT1A is located in the mitochondrial outer membrane. Reason: CPT1A is a polytopic mitochondrial outer membrane protein with two TM segments, cytosolic N- and C-termini and an intermembrane-space loop; this is where its catalytic activity is exercised. Supporting Evidence: file:rat/Cpt1a/Cpt1a-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion outer membrane |
| GO:0005741 mitochondrial outer membrane | ISO GO_REF:0000121 | ACCEPT | Summary: CPT1A is located in the mitochondrial outer membrane. Reason: CPT1A is a polytopic mitochondrial outer membrane protein with two TM segments, cytosolic N- and C-termini and an intermembrane-space loop; this is where its catalytic activity is exercised. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P50416 · CPT1A (human) SUPPORTS TRANSFER Same outer-membrane topology in human CPT1A. Supporting Evidence: file:rat/Cpt1a/Cpt1a-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion outer membrane |
| GO:0005789 endoplasmic reticulum membrane | IDA NOT PMID:12401113 The liver isoform of carnitine palmitoyltransferase 1 is not... | ACCEPT | Summary: NOT located in ER membrane: L-CPT1 is not targeted to the ER. Reason: Broadway et al. showed GFP-tagged L-CPT1 in mitochondria but not ER, no authentic insertion into microsomes, and attributed microsomal CPT activity to mitochondrial contamination. The negative annotation is well supported and useful because CPT1C (not CPT1A) is the ER isoform. Supporting Evidence: PMID:12401113 It is concluded that L-CPT1 is not targeted to the ER membrane |
| GO:0006006 glucose metabolic process | IMP PMID:12754501 Inhibition of hypothalamic carnitine palmitoyltransferase-1 ... | MARK AS OVER ANNOTATED | Summary: Hypothalamic CPT1 inhibition reduced endogenous (hepatic) glucose production. Reason: The phenotype is a systemic, centrally mediated effect: reduced lipid oxidation in hypothalamic neurons alters nutrient sensing and hence hepatic glucose output. CPT1A does not carry out any step of glucose metabolism; the annotation records a downstream physiological consequence. Supporting Evidence: PMID:12754501 Either genetic or biochemical inhibition of hypothalamic CPT1 activity was sufficient to substantially diminish food intake and endogenous glucose production. file:rat/Cpt1a/Cpt1a-deep-research-manual.md systemic consequences of altered neuronal lipid |
| GO:0006631 fatty acid metabolic process | IBA GO_REF:0000033 | MODIFY | Summary: CPT1A participates in fatty acid metabolism. Reason: True but general: CPT1A acts specifically on long-chain acyl-CoAs, and the gene already carries the more specific GO:0001676 long-chain fatty acid metabolic process (and GO:0006635 fatty acid beta-oxidation). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN001097100 · PANTHER:PTN001097100 SUPPORTS TRANSFER Correct for the CPT1 clade, but the node term is coarser than the long-chain specificity shared by all members. Proposed replacements: long-chain fatty acid metabolic process Supporting Evidence: file:rat/Cpt1a/Cpt1a-uniprot.txt Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion |
| GO:0006631 fatty acid metabolic process | IDA PMID:24222496 Comparison of the catalytic activities of three isozymes of ... | MODIFY | Summary: CPT1A participates in fatty acid metabolism. Reason: True but general: CPT1A acts specifically on long-chain acyl-CoAs, and the gene already carries the more specific GO:0001676 long-chain fatty acid metabolic process (and GO:0006635 fatty acid beta-oxidation). Proposed replacements: long-chain fatty acid metabolic process Supporting Evidence: PMID:24222496 The enzyme carnitine palmitoyltransferase 1 (CPT1) catalyzes the transfer of an acyl group from acyl-CoA to carnitine to form acylcarnitine |
| GO:0006631 fatty acid metabolic process | IEP PMID:30851372 Protective effect and mechanism of Qiwei Tiexie capsule on 3... | MODIFY | Summary: CPT1A participates in fatty acid metabolism. Reason: True but general: CPT1A acts specifically on long-chain acyl-CoAs, and the gene already carries the more specific GO:0001676 long-chain fatty acid metabolic process (and GO:0006635 fatty acid beta-oxidation). This row is an expression (IEP) observation in adipocytes; the process claim itself is upheld from the biochemistry. Proposed replacements: long-chain fatty acid metabolic process Supporting Evidence: PMID:30851372 The expression levels of carnitine palmitoyltransferase-1 (CPT-1) file:rat/Cpt1a/Cpt1a-uniprot.txt Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion |
| GO:0006631 fatty acid metabolic process | IEP PMID:31639005 Therapeutic effect and autophagy regulation of myriocin in n... | MODIFY | Summary: CPT1A participates in fatty acid metabolism. Reason: True but general: CPT1A acts specifically on long-chain acyl-CoAs, and the gene already carries the more specific GO:0001676 long-chain fatty acid metabolic process (and GO:0006635 fatty acid beta-oxidation). This row is an expression (IEP) observation; the process claim itself is upheld from the biochemistry. Proposed replacements: long-chain fatty acid metabolic process Supporting Evidence: PMID:31639005 carnitine palmitoyl transferase-1α(Cpt-1α) and acyl CoA oxidase-2 (Acox-2) file:rat/Cpt1a/Cpt1a-uniprot.txt Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion |
| GO:0006635 fatty acid beta-oxidation | IEA GO_REF:0000041 | ACCEPT | Summary: CPT1A is part of mitochondrial fatty acid beta-oxidation. Reason: CPT1A catalyses the rate-limiting, malonyl-CoA-regulated entry step for long-chain fatty acids into mitochondrial beta-oxidation; adenoviral overexpression in rat hepatocytes and liver raises beta-oxidation flux. Supporting Evidence: file:rat/Cpt1a/Cpt1a-uniprot.txt Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion PMID:18349115 Overexpression of CPT-1a increased the rate of beta-oxidation and ketogenesis by approximately 70% PMID:21990363 The enzyme carnitine palmitoyltransferase 1 (CPT1), which is anchored in the outer mitochondrial membrane (OMM), controls the rate-limiting step in fatty acid β-oxidation in mammalian tissues. |
| GO:0006635 fatty acid beta-oxidation | IEP PMID:31901136 Modulation effects of black-vinegar-based supplement against... | ACCEPT | Summary: CPT1A is part of mitochondrial fatty acid beta-oxidation. Reason: CPT1A catalyses the rate-limiting, malonyl-CoA-regulated entry step for long-chain fatty acids into mitochondrial beta-oxidation; adenoviral overexpression in rat hepatocytes and liver raises beta-oxidation flux. This specific row is IEP (expression change); the process claim is upheld on the biochemical evidence. Supporting Evidence: file:rat/Cpt1a/Cpt1a-uniprot.txt Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion PMID:18349115 Overexpression of CPT-1a increased the rate of beta-oxidation and ketogenesis by approximately 70% PMID:21990363 The enzyme carnitine palmitoyltransferase 1 (CPT1), which is anchored in the outer mitochondrial membrane (OMM), controls the rate-limiting step in fatty acid β-oxidation in mammalian tissues. |
| GO:0006635 fatty acid beta-oxidation | IEP PMID:31953200 Study on the protection of water extracts of Polygoni Multif... | ACCEPT | Summary: CPT1A is part of mitochondrial fatty acid beta-oxidation. Reason: CPT1A catalyses the rate-limiting, malonyl-CoA-regulated entry step for long-chain fatty acids into mitochondrial beta-oxidation; adenoviral overexpression in rat hepatocytes and liver raises beta-oxidation flux. This specific row is IEP (expression/activity change); the process claim is upheld on the biochemical evidence. Supporting Evidence: file:rat/Cpt1a/Cpt1a-uniprot.txt Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion PMID:18349115 Overexpression of CPT-1a increased the rate of beta-oxidation and ketogenesis by approximately 70% PMID:21990363 The enzyme carnitine palmitoyltransferase 1 (CPT1), which is anchored in the outer mitochondrial membrane (OMM), controls the rate-limiting step in fatty acid β-oxidation in mammalian tissues. PMID:31953200 PMRWE and PMRPWE increased the decreased liver CPT1A enzymatic activity in HFD-fed rats. |
| GO:0006641 triglyceride metabolic process | IMP PMID:18349115 A moderate increase in carnitine palmitoyltransferase 1a act... | KEEP AS NON CORE | Summary: CPT1A overexpression lowers hepatic triglyceride content and secretion. Reason: Increasing CPT1A diverts long-chain acyl-CoA from esterification to oxidation, lowering TG. A real, physiologically important consequence of its core activity, but CPT1A performs no step of TG synthesis or breakdown; non-core. Supporting Evidence: PMID:18349115 CPT-1a overexpression was accompanied by a 35% reduction in TG accumulation and a 60% decrease in TG secretion by hepatocytes file:rat/Cpt1a/Cpt1a-uniprot.txt Plays an important role in hepatic triglyceride metabolism |
| GO:0007584 response to nutrient | IEP PMID:33310031 WY14643 improves left ventricular myocardial mitochondrial a... | KEEP AS NON CORE | Summary: Cpt1a expression is altered in response to nutritional state. Reason: Expression-pattern (IEP) annotation: the study reports that Cpt1a mRNA/protein/activity changes under this condition. This is a genuine but peripheral observation about regulation of Cpt1a expression (largely via PPARalpha) rather than a function of the protein; kept as non-core. Supporting Evidence: PMID:33310031 WY14643 upregulated PPARα, PGC1α, and CPT1α, and downregulated ACC2. |
| GO:0009410 response to xenobiotic stimulus | IEP PMID:19553925 Nonalcoholic hepatic steatosis in Zucker diabetic rats: spon... | KEEP AS NON CORE | Summary: Cpt1 mRNA induced by fenofibrate in ZDF rat liver. Reason: Expression-pattern (IEP) annotation: the study reports that Cpt1a mRNA/protein/activity changes under this condition. This is a genuine but peripheral observation about regulation of Cpt1a expression (largely via PPARalpha) rather than a function of the protein; kept as non-core. Supporting Evidence: PMID:19553925 Acyl-CoA oxidase (ACO) and carnitine palmitoyltransferase I (CPTI) mRNA levels were increased by fenofibrate |
| GO:0009410 response to xenobiotic stimulus | IEP PMID:31748600 PCSK9 inhibition as a novel therapeutic target for alcoholic... | KEEP AS NON CORE | Summary: Cpt1 mRNA changes with alcohol/alirocumab treatment. Reason: Expression-pattern (IEP) annotation: the study reports that Cpt1a mRNA/protein/activity changes under this condition. This is a genuine but peripheral observation about regulation of Cpt1a expression (largely via PPARalpha) rather than a function of the protein; kept as non-core. Supporting Evidence: PMID:31748600 alcohol exposure down-regulated mRNA expression of peroxisome proliferator-activated receptor alpha (PPARα) and carnitine palmitoyltransferase I (CPT1) |
| GO:0009410 response to xenobiotic stimulus | IEP PMID:31953200 Study on the protection of water extracts of Polygoni Multif... | KEEP AS NON CORE | Summary: Cpt1a expression/activity increased by Polygoni Multiflori extracts. Reason: Expression-pattern (IEP) annotation: the study reports that Cpt1a mRNA/protein/activity changes under this condition. This is a genuine but peripheral observation about regulation of Cpt1a expression (largely via PPARalpha) rather than a function of the protein; kept as non-core. Supporting Evidence: PMID:31953200 including the key enzyme carnitine palmitoyltransferase 1A (CPT1A) |
| GO:0009437 carnitine metabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: CPT1A converts carnitine to long-chain acylcarnitines. Reason: CPT1A consumes L-carnitine to form acylcarnitine, a direct chemical step of carnitine metabolism. Accepted, consistent with the human CPT1A review. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001097100 · PANTHER:PTN001097100 SUPPORTS TRANSFER All CPT1 clade members use carnitine as acyl acceptor. Supporting Evidence: file:rat/Cpt1a/Cpt1a-uniprot.txt Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion PMID:24222496 The enzyme carnitine palmitoyltransferase 1 (CPT1) catalyzes the transfer of an acyl group from acyl-CoA to carnitine to form acylcarnitine |
| GO:0009437 carnitine metabolic process | IDA PMID:21990363 An environment-dependent structural switch underlies the reg... | ACCEPT | Summary: CPT1A converts carnitine to long-chain acylcarnitines. Reason: CPT1A consumes L-carnitine to form acylcarnitine, a direct chemical step of carnitine metabolism. Accepted, consistent with the human CPT1A review. Supporting Evidence: file:rat/Cpt1a/Cpt1a-uniprot.txt Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion PMID:24222496 The enzyme carnitine palmitoyltransferase 1 (CPT1) catalyzes the transfer of an acyl group from acyl-CoA to carnitine to form acylcarnitine |
| GO:0009437 carnitine metabolic process | IDA PMID:24222496 Comparison of the catalytic activities of three isozymes of ... | ACCEPT | Summary: CPT1A converts carnitine to long-chain acylcarnitines. Reason: CPT1A consumes L-carnitine to form acylcarnitine, a direct chemical step of carnitine metabolism. Accepted, consistent with the human CPT1A review. Supporting Evidence: file:rat/Cpt1a/Cpt1a-uniprot.txt Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion PMID:24222496 The enzyme carnitine palmitoyltransferase 1 (CPT1) catalyzes the transfer of an acyl group from acyl-CoA to carnitine to form acylcarnitine |
| GO:0009437 carnitine metabolic process | IEA GO_REF:0000120 | ACCEPT | Summary: CPT1A converts carnitine to long-chain acylcarnitines. Reason: CPT1A consumes L-carnitine to form acylcarnitine, a direct chemical step of carnitine metabolism. Accepted, consistent with the human CPT1A review. Supporting Evidence: file:rat/Cpt1a/Cpt1a-uniprot.txt Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion PMID:24222496 The enzyme carnitine palmitoyltransferase 1 (CPT1) catalyzes the transfer of an acyl group from acyl-CoA to carnitine to form acylcarnitine |
| GO:0009437 carnitine metabolic process | ISO GO_REF:0000121 | ACCEPT | Summary: CPT1A converts carnitine to long-chain acylcarnitines. Reason: CPT1A consumes L-carnitine to form acylcarnitine, a direct chemical step of carnitine metabolism. Accepted, consistent with the human CPT1A review. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P50416 · CPT1A (human) SUPPORTS TRANSFER Same reaction in human CPT1A. Supporting Evidence: file:rat/Cpt1a/Cpt1a-uniprot.txt Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion PMID:24222496 The enzyme carnitine palmitoyltransferase 1 (CPT1) catalyzes the transfer of an acyl group from acyl-CoA to carnitine to form acylcarnitine |
| GO:0009437 carnitine metabolic process | TAS PMID:12826662 A single amino acid change (substitution of the conserved Gl... | ACCEPT | Summary: CPT1A converts carnitine to long-chain acylcarnitines. Reason: CPT1A consumes L-carnitine to form acylcarnitine, a direct chemical step of carnitine metabolism. Accepted, consistent with the human CPT1A review. Supporting Evidence: PMID:12826662 Carnitine palmitoyltransferase I (CPTI) catalyzes the conversion of long-chain fatty acyl-CoAs to acylcarnitines in the presence of l-carnitine. |
| GO:0016746 acyltransferase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO acyltransferase activity from the carnitine/choline acyltransferase domain. Reason: Correct but general; the specific activity, carnitine O-palmitoyltransferase activity (GO:0004095), is experimentally established and already carried by the gene. Proposed replacements: carnitine O-palmitoyltransferase activity Supporting Evidence: file:rat/Cpt1a/Cpt1a-uniprot.txt Belongs to the carnitine/choline acetyltransferase family PMID:24222496 The enzyme carnitine palmitoyltransferase 1 (CPT1) catalyzes the transfer of an acyl group from acyl-CoA to carnitine to form acylcarnitine |
| GO:0030674 protein-macromolecule adaptor activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Adaptor activity recruiting ZDHHC4 to MAVS (by similarity to human). Reason: Transferred from human CPT1A, reported to recruit ZDHHC4 to MAVS so sustaining type I IFN signalling. The orthology transfer is plausible but untested in rat, rests on a single human study, and is peripheral to the enzymatic core; kept as non-core. Supporting Evidence: file:rat/Cpt1a/Cpt1a-uniprot.txt Sustains the IFN-I response by recruiting ZDHCC4 to palmitoylate MAVS at the mitochondria leading to MAVS stabilization and activation |
| GO:0030674 protein-macromolecule adaptor activity | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Adaptor activity recruiting ZDHHC4 to MAVS (by similarity to human). Reason: Transferred from human CPT1A, reported to recruit ZDHHC4 to MAVS so sustaining type I IFN signalling. The orthology transfer is plausible but untested in rat, rests on a single human study, and is peripheral to the enzymatic core; kept as non-core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P50416 · CPT1A (human) SUPPORTS TRANSFER Human IDA (PMID:38016475); rat not tested. Supporting Evidence: file:rat/Cpt1a/Cpt1a-uniprot.txt Sustains the IFN-I response by recruiting ZDHCC4 to palmitoylate MAVS at the mitochondria leading to MAVS stabilization and activation |
| GO:0030855 epithelial cell differentiation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Epithelial cell differentiation transferred from human expression data. Reason: The human source annotation (PMID:21492153) is IEP, i.e. CPT1A expression changes during epithelial differentiation. Expression during a process does not show that CPT1A performs part of it, and transferring an expression observation by orthology adds further distance. Over-annotation. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:P50416 · CPT1A (human) SOURCE WEAK OR INFERRED Source is an IEP expression annotation on human CPT1A. |
| GO:0030855 epithelial cell differentiation | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Epithelial cell differentiation transferred from human expression data. Reason: The human source annotation (PMID:21492153) is IEP, i.e. CPT1A expression changes during epithelial differentiation. Expression during a process does not show that CPT1A performs part of it, and transferring an expression observation by orthology adds further distance. Over-annotation. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:P50416 · CPT1A (human) SOURCE WEAK OR INFERRED Source is an IEP expression annotation on human CPT1A. |
| GO:0031667 response to nutrient levels | IEP PMID:30851372 Protective effect and mechanism of Qiwei Tiexie capsule on 3... | KEEP AS NON CORE | Summary: Cpt1a expression changes with diet/nutritional status in rat models. Reason: Expression-pattern (IEP) annotation: the study reports that Cpt1a mRNA/protein/activity changes under this condition. This is a genuine but peripheral observation about regulation of Cpt1a expression (largely via PPARalpha) rather than a function of the protein; kept as non-core. Supporting Evidence: PMID:30851372 The expression levels of carnitine palmitoyltransferase-1 (CPT-1) |
| GO:0031667 response to nutrient levels | IEP PMID:30868489 Berberine Ameliorates High-Fat Diet-Induced Non-Alcoholic Fa... | KEEP AS NON CORE | Summary: Cpt1a expression changes with diet/nutritional status in rat models. Reason: Expression-pattern (IEP) annotation: the study reports that Cpt1a mRNA/protein/activity changes under this condition. This is a genuine but peripheral observation about regulation of Cpt1a expression (largely via PPARalpha) rather than a function of the protein; kept as non-core. Supporting Evidence: PMID:30868489 the protein expression levels of SIRT3, p-AMPK, p-ACC, and CPT-1A in the liver were significantly decreased compared to those in the NC group |
| GO:0031667 response to nutrient levels | IEP PMID:31639005 Therapeutic effect and autophagy regulation of myriocin in n... | KEEP AS NON CORE | Summary: Cpt1a expression changes with diet/nutritional status in rat models. Reason: Expression-pattern (IEP) annotation: the study reports that Cpt1a mRNA/protein/activity changes under this condition. This is a genuine but peripheral observation about regulation of Cpt1a expression (largely via PPARalpha) rather than a function of the protein; kept as non-core. Supporting Evidence: PMID:31639005 carnitine palmitoyl transferase-1α(Cpt-1α) and acyl CoA oxidase-2 (Acox-2) |
| GO:0031667 response to nutrient levels | IEP PMID:31901136 Modulation effects of black-vinegar-based supplement against... | KEEP AS NON CORE | Summary: Cpt1a expression changes with diet/nutritional status in rat models. Reason: Expression-pattern (IEP) annotation: the study reports that Cpt1a mRNA/protein/activity changes under this condition. This is a genuine but peripheral observation about regulation of Cpt1a expression (largely via PPARalpha) rather than a function of the protein; kept as non-core. Supporting Evidence: PMID:31901136 A similar effect was observed for AMPK, peroxisome proliferator-activated receptor alpha, retinoid X receptor alpha, CPT1, and UCP2 gene and protein levels in livers |
| GO:0031667 response to nutrient levels | IEP PMID:31930271 The preventive effect of phenolic-rich extracts from Chinese... | KEEP AS NON CORE | Summary: Cpt1a expression changes with diet/nutritional status in rat models. Reason: Expression-pattern (IEP) annotation: the study reports that Cpt1a mRNA/protein/activity changes under this condition. This is a genuine but peripheral observation about regulation of Cpt1a expression (largely via PPARalpha) rather than a function of the protein; kept as non-core. Supporting Evidence: PMID:31930271 upregulating the expression levels of p-AMPK, PPAR-α, CPT1 and Bcl-2 |
| GO:0031667 response to nutrient levels | IEP PMID:31953200 Study on the protection of water extracts of Polygoni Multif... | KEEP AS NON CORE | Summary: Cpt1a expression changes with diet/nutritional status in rat models. Reason: Expression-pattern (IEP) annotation: the study reports that Cpt1a mRNA/protein/activity changes under this condition. This is a genuine but peripheral observation about regulation of Cpt1a expression (largely via PPARalpha) rather than a function of the protein; kept as non-core. Supporting Evidence: PMID:31953200 including the key enzyme carnitine palmitoyltransferase 1A (CPT1A) |
| GO:0031998 regulation of fatty acid beta-oxidation | TAS PMID:11087756 The N-terminal domain of rat liver carnitine palmitoyltransf... | MARK AS OVER ANNOTATED | Summary: CPT1A controls the rate of fatty acid beta-oxidation. Reason: CPT1A is the regulated, rate-limiting enzyme of mitochondrial long-chain fatty acid oxidation, not a regulator of the pathway. Raising its amount or relieving malonyl-CoA inhibition increases flux because the enzyme itself performs a step; that participation is already captured by GO:0006635 fatty acid beta-oxidation. Annotating the enzyme to regulation of its own pathway is an over-annotation. Supporting Evidence: PMID:21622568 CPT1a (carnitine palmitoyltransferase 1a) in the liver mitochondrial outer membrane (MOM) catalyzes the primary regulated step in overall mitochondrial fatty acid oxidation. |
| GO:0032000 positive regulation of fatty acid beta-oxidation | IMP PMID:19302064 Modulation of the hepatic malonyl-CoA-carnitine palmitoyltra... | MARK AS OVER ANNOTATED | Summary: CPT1A overexpression (wt or M593S) sustained hepatocyte beta-oxidation under high glucose/insulin. Reason: CPT1A is the regulated, rate-limiting enzyme of mitochondrial long-chain fatty acid oxidation, not a regulator of the pathway. Raising its amount or relieving malonyl-CoA inhibition increases flux because the enzyme itself performs a step; that participation is already captured by GO:0006635 fatty acid beta-oxidation. Annotating the enzyme to regulation of its own pathway is an over-annotation. Supporting Evidence: PMID:19302064 counteracted the inhibition of oleate beta-oxidation induced by 20 mM glucose/10 nM insulin |
| GO:0042755 eating behavior | IMP PMID:12754501 Inhibition of hypothalamic carnitine palmitoyltransferase-1 ... | KEEP AS NON CORE | Summary: Hypothalamic CPT1 knockdown/inhibition decreased food intake. Reason: Ribozyme knockdown and pharmacological inhibition in rat hypothalamus reduced food intake, implicating neuronal long-chain fatty acid oxidation in nutrient sensing. Indirect, tissue-specific physiological role; non-core. Note that the pharmacological inhibitors do not distinguish CPT1A from CPT1C. Supporting Evidence: PMID:12754501 Either genetic or biochemical inhibition of hypothalamic CPT1 activity was sufficient to substantially diminish food intake and endogenous glucose production. |
| GO:0042802 identical protein binding | IPI PMID:19136561 Self-association of transmembrane domain 2 (TM2), but not TM... | KEEP AS NON CORE | Summary: CPT1A self-associates into trimers/hexamers via TM2. Reason: Oligomerisation (hexamer in liver mitochondria, trimer/hexamer equilibrium; TM2 GXXXG motifs) is well documented and may underlie function, but is a structural property rather than the core activity. Supporting Evidence: PMID:19136561 The data indicate that in liver mitochondria in vivo CPT1A exists as a hexamer file:rat/Cpt1a/Cpt1a-uniprot.txt Homohexamer and homotrimer |
| GO:0043279 response to alkaloid | IEP PMID:30868489 Berberine Ameliorates High-Fat Diet-Induced Non-Alcoholic Fa... | KEEP AS NON CORE | Summary: Hepatic CPT-1A protein changes with berberine treatment. Reason: Expression-pattern (IEP) annotation: the study reports that Cpt1a mRNA/protein/activity changes under this condition. This is a genuine but peripheral observation about regulation of Cpt1a expression (largely via PPARalpha) rather than a function of the protein; kept as non-core. Supporting Evidence: PMID:30868489 the protein expression levels of SIRT3, p-AMPK, p-ACC, and CPT-1A in the liver were significantly decreased compared to those in the NC group |
| GO:0045089 positive regulation of innate immune response | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of innate immune response via MAVS palmitoylation (by similarity). Reason: Transferred from human CPT1A, reported to recruit ZDHHC4 to MAVS so sustaining type I IFN signalling. The orthology transfer is plausible but untested in rat, rests on a single human study, and is peripheral to the enzymatic core; kept as non-core. Supporting Evidence: file:rat/Cpt1a/Cpt1a-uniprot.txt Sustains the IFN-I response by recruiting ZDHCC4 to palmitoylate MAVS at the mitochondria leading to MAVS stabilization and activation |
| GO:0045089 positive regulation of innate immune response | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of innate immune response via MAVS palmitoylation (by similarity). Reason: Transferred from human CPT1A, reported to recruit ZDHHC4 to MAVS so sustaining type I IFN signalling. The orthology transfer is plausible but untested in rat, rests on a single human study, and is peripheral to the enzymatic core; kept as non-core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P50416 · CPT1A (human) SUPPORTS TRANSFER Human IDA (PMID:38016475); rat not tested. Supporting Evidence: file:rat/Cpt1a/Cpt1a-uniprot.txt Sustains the IFN-I response by recruiting ZDHCC4 to palmitoylate MAVS at the mitochondria leading to MAVS stabilization and activation |
| GO:0045471 response to ethanol | IEP PMID:27939985 Dihydroartemisinin protects against alcoholic liver injury t... | KEEP AS NON CORE | Summary: Cpt1a expression changes in alcoholic liver injury model. Reason: Expression-pattern (IEP) annotation: the study reports that Cpt1a mRNA/protein/activity changes under this condition. This is a genuine but peripheral observation about regulation of Cpt1a expression (largely via PPARalpha) rather than a function of the protein; kept as non-core. The cached record is abstract-only and does not mention CPT1; deferring to the curator who read the full text. |
| GO:0046320 regulation of fatty acid oxidation | IMP PMID:11988095 Adenovirus-mediated overexpression of liver carnitine palmit... | MARK AS OVER ANNOTATED | Summary: CPT1A overexpression in INS1E cells increased fatty acid oxidation. Reason: CPT1A is the regulated, rate-limiting enzyme of mitochondrial long-chain fatty acid oxidation, not a regulator of the pathway. Raising its amount or relieving malonyl-CoA inhibition increases flux because the enzyme itself performs a step; that participation is already captured by GO:0006635 fatty acid beta-oxidation. Annotating the enzyme to regulation of its own pathway is an over-annotation. Supporting Evidence: PMID:11988095 a 6-fold increase in the CPT activity, and an increase in fatty acid oxidation |
| GO:0050796 regulation of insulin secretion | IMP PMID:11988095 Adenovirus-mediated overexpression of liver carnitine palmit... | KEEP AS NON CORE | Summary: CPT1A overexpression in INS1E beta-cells lowers glucose-stimulated insulin secretion. Reason: Elevated CPT1A activity depletes a lipid signal needed for GSIS (rescued by palmitate; normalised by etomoxir). The authors conclude CPT1 activity regulates insulin secretion; this is an indirect metabolic effect on a beta-cell-specific process, kept as non-core. Supporting Evidence: PMID:11988095 These results provide further evidence that CPT I activity regulates insulin secretion in the beta-cell. |
| GO:0071398 cellular response to fatty acid | IEP PMID:19332540 Palmitate induces insulin resistance in H4IIEC3 hepatocytes ... | KEEP AS NON CORE | Summary: Palmitate induces Cpt1a gene expression in H4IIEC3 hepatocytes. Reason: Full text read: palmitate but not oleate increased CPT-1a mRNA, and etomoxir reduced palmitate-induced ROS. This is an expression response to fatty acid, consistent with substrate-driven induction; non-core. Supporting Evidence: PMID:19332540 palmitate, but not oleate, significantly increased expression of the CPT-1a gene |
| GO:0097421 liver regeneration | IEP PMID:31953200 Study on the protection of water extracts of Polygoni Multif... | MARK AS OVER ANNOTATED | Summary: Liver CPT1A expression/activity restored by herbal extracts in HFD-fed rats. Reason: The study is about diet-induced steatosis and its reversal, not liver regeneration (regrowth after loss of tissue). An expression change in this setting does not show participation in liver regeneration. Supporting Evidence: PMID:31953200 PMRWE and PMRPWE increased the decreased liver CPT1A enzymatic activity in HFD-fed rats. |
| GO:1904772 response to tetrachloromethane | IEP PMID:31918260 Hepatoprotective effect of different combinations of 18α-and... | KEEP AS NON CORE | Summary: Cpt-1a mRNA altered in CCl4-induced liver injury. Reason: Expression-pattern (IEP) annotation: the study reports that Cpt1a mRNA/protein/activity changes under this condition. This is a genuine but peripheral observation about regulation of Cpt1a expression (largely via PPARalpha) rather than a function of the protein; kept as non-core. Supporting Evidence: PMID:31918260 via regulating the mRNA levels of SREBP-1c, ACC, PPAR-α, and CPT-1a |
| GO:0006853 carnitine shuttle | IC PMID:24222496 Comparison of the catalytic activities of three isozymes of ... | NEW | Summary: CPT1A catalyses the first step of the carnitine shuttle. Reason: The carnitine shuttle moves long-chain fatty acids into mitochondria via CPT1 (acylcarnitine formation at the outer membrane), carnitine-acylcarnitine translocase and CPT2. Rat CPT1A has experimentally established carnitine O-palmitoyltransferase activity at the outer membrane, so it performs a step of this process. Comparator check: human CPT1A, CPT2 and SLC25A20 carry GO:0006853, i.e. the term is used for the enzymes and transporter that do the steps. Not an ancestor/descendant of any other term carried. Supporting Evidence: file:rat/Cpt1a/Cpt1a-uniprot.txt Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion PMID:24222496 The enzyme carnitine palmitoyltransferase 1 (CPT1) catalyzes the transfer of an acyl group from acyl-CoA to carnitine to form acylcarnitine PMID:9461513 Carnitine palmitoyltransferase I (CPTI) catalyses the transfer of long chain fatty acids to carnitine for translocation across the mitochondrial inner membrane. |
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Download this section (compressed HTML)Q: Does rat CPT1A have the peptide-lysine succinyltransferase activity reported for human CPT1A, and is it separable from carnitine acyltransfer (e.g. G710E)?
Q: Should the "regulation of fatty acid (beta-)oxidation" annotations to CPT1A be retired, given that CPT1A is the regulated enzyme of the pathway rather than an upstream regulator?
Q: Is the ZDHHC4-MAVS adaptor role of CPT1A conserved in rodents?
Experiment: Assay recombinant rat CPT1A (wild type and a carnitine-transfer-dead mutant) for succinyl-CoA-dependent lysine succinylation of ENO1 in vitro and in hepatocytes.
Experiment: Test whether rat Cpt1a knockdown in macrophages or hepatocytes reduces MAVS palmitoylation and type I IFN responses after RNA-virus challenge.
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