CPT1A is a malonyl-CoA-sensitive carnitine acyltransferase of the mitochondrial outer membrane. It converts long-chain acyl-CoA and L-carnitine into acylcarnitine and CoA, supplying the carnitine shuttle and mitochondrial fatty-acid oxidation. This catalytic entry step links lipid utilization to nutritional state; inherited loss of function causes CPT1A deficiency with impaired fasting adaptation and hypoketotic hypoglycemia. CPT1A also has experimentally demonstrated peptide-lysine succinyltransferase activity, including ENO1 modification, and a reported adaptor role recruiting ZDHHC4 to MAVS to sustain innate immune signaling. Its two human protein products differ at their C termini; equivalent full-length activity of both products has not been established.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004095 carnitine O-palmitoyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: The ancestral carnitine acyl-transfer activity is retained in human CPT1A. Reason: The actual PTHR22589 tree places human P50416 below PTN001097100, whose current IBD explicitly assigns GO:0004095; no loss record lies on the target path. The target MSA reconstructs the official 773-residue sequence. Human enzyme expressed in yeast and endogenous human fibroblast assays independently establish the reaction. The target's inclusion among descendant experimental sources is legitimate phylogenetic evidence. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001097100 SUPPORTS TRANSFER Actual PTN001097100 IBD is on the human target path; the MSA matches official P50416 and no target-path loss record is present. Descendant evidence is context, not a pairwise-transfer substitute. Supporting Evidence: file:human/CPT1A/CPT1A-source-evidence.yaml |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | MODIFY | Summary: Refine the valid ancestral mitochondrial location to the outer membrane. Reason: The current PTN001097100 mitochondrial IBD is on the target path and remains valid. Human CPT1A enzymology, mitochondrial membrane preparations and established topology support the more specific outer membrane. This is target-level precision, not a claim that the ancestral placement was wrong or that CPT1A occurs exclusively in one context. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: PANTHER:PTN001097100 SUPPORTS TRANSFER Actual PTN001097100 IBD is on the human target path; the MSA matches official P50416 and no target-path loss record is present. Descendant evidence is context, not a pairwise-transfer substitute. Proposed replacements: mitochondrial outer membrane Supporting Evidence: file:human/CPT1A/CPT1A-source-evidence.yaml |
| GO:0006631 fatty acid metabolic process | IBA GO_REF:0000033 | MODIFY | Summary: Specify the long-chain substrates of the conserved fatty-acid metabolic role. Reason: The actual ancestral GO:0006631 IBD at PTN001097100 is inherited by CPT1A. Human CPT1A transfers long-chain acyl groups to carnitine; palmitoyl-CoA is directly assayed in the canonical literature. GO:0001676 captures this substrate scope more precisely without denying the broader inherited pathway assertion. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: PANTHER:PTN001097100 SUPPORTS TRANSFER Actual PTN001097100 IBD is on the human target path; the MSA matches official P50416 and no target-path loss record is present. Descendant evidence is context, not a pairwise-transfer substitute. Proposed replacements: long-chain fatty acid metabolic process Supporting Evidence: file:human/CPT1A/CPT1A-source-evidence.yaml |
| GO:0009437 carnitine metabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: CPT1A directly metabolizes carnitine by forming acylcarnitine. Reason: The current GO:0009437 IBD at PTN001097100 lies on the target path with legitimate human and rat descendant evidence. Carnitine is a substrate in the directly measured acyl-transfer reaction, so this is performed metabolism rather than merely a requirement for transport. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001097100 SUPPORTS TRANSFER Actual PTN001097100 IBD is on the human target path; the MSA matches official P50416 and no target-path loss record is present. Descendant evidence is context, not a pairwise-transfer substitute. Supporting Evidence: file:human/CPT1A/CPT1A-source-evidence.yaml |
| GO:0004095 carnitine O-palmitoyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: The combined electronic sources correctly identify the canonical acyl-transfer reaction. Reason: The complete current source object includes the reaction, enzyme classification and ARBA evidence. Official Rhea:12661 and EC 2.3.1.21 match GO:0004095, while the actual current ARBA00087538 branch 0 matches the target's FunFam and eukaryotic lineage. Direct human enzymology independently supports the biological conclusion; a present-day branch match is not a reconstructed historical rule run. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00087538 SUPPORTS TRANSFER Current rule/reaction applicability is reconstructed from official target identifiers and taxonomy. It is not a replay of the historical electronic inference. UniProtKB:P32198 SUPPORTS TRANSFER Current rule/reaction applicability is reconstructed from official target identifiers and taxonomy. It is not a replay of the historical electronic inference. ensembl:ENSRNOP00000019652 SUPPORTS TRANSFER Current rule/reaction applicability is reconstructed from official target identifiers and taxonomy. It is not a replay of the historical electronic inference. UniProtKB:P97742 SUPPORTS TRANSFER Current rule/reaction applicability is reconstructed from official target identifiers and taxonomy. It is not a replay of the historical electronic inference. ensembl:ENSMUSP00000025835 SUPPORTS TRANSFER Current rule/reaction applicability is reconstructed from official target identifiers and taxonomy. It is not a replay of the historical electronic inference. RHEA:12661 SUPPORTS TRANSFER Current rule/reaction applicability is reconstructed from official target identifiers and taxonomy. It is not a replay of the historical electronic inference. EC:2.3.1.21 SUPPORTS TRANSFER Current rule/reaction applicability is reconstructed from official target identifiers and taxonomy. It is not a replay of the historical electronic inference. Supporting Evidence: file:human/CPT1A/CPT1A-source-evidence.yaml |
| GO:0005741 mitochondrial outer membrane | IEA GO_REF:0000120 | ACCEPT | Summary: The combined electronic mitochondrial outer-membrane assignment is correct. Reason: The two transmembrane segments and experimentally grounded membrane context support GO:0005741. Current ARBA00088384 branch 11 matches both official target FunFams and Haplorrhini. The exact current sources are preserved separately from the historical row's omitted WITH/FROM list; neither rule matching nor predicted helices alone substitutes for the experimental context. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00088384 SUPPORTS TRANSFER Current rule/reaction applicability is reconstructed from official target identifiers and taxonomy. It is not a replay of the historical electronic inference. UniProtKB:P32198 SUPPORTS TRANSFER Current rule/reaction applicability is reconstructed from official target identifiers and taxonomy. It is not a replay of the historical electronic inference. ensembl:ENSRNOP00000019652 SUPPORTS TRANSFER Current rule/reaction applicability is reconstructed from official target identifiers and taxonomy. It is not a replay of the historical electronic inference. UniProtKB-SubCell:SL-0172 SUPPORTS TRANSFER Current rule/reaction applicability is reconstructed from official target identifiers and taxonomy. It is not a replay of the historical electronic inference. Supporting Evidence: file:human/CPT1A/CPT1A-source-evidence.yaml |
| GO:0006853 carnitine shuttle | IEA GO_REF:0000117 | ACCEPT | Summary: The historical carnitine-shuttle assertion is biologically correct although no longer active in current GOA. Reason: CPT1A catalyzes the acylcarnitine-forming step explicitly included in the definition of the carnitine shuttle. The historical source object is retained with retired metadata because its exact assertion is absent from the current seed. Retirement is source reconciliation, not biological rejection; no unavailable historical ARBA branch has been invented. Propagation Review Root cause: NO FAILURE CORE Sources checked: GO_REF:0000117 SOURCE STALE OR MISSING The exact historical assertion is absent from current GOA. The historical ARBA premise was not reconstructed; independent biology supports the retained shuttle assertion. Supporting Evidence: file:human/CPT1A/CPT1A-source-evidence.yaml |
| GO:0016746 acyltransferase activity | IEA GO_REF:0000002 | MODIFY | Summary: Refine the InterPro acyltransferase assertion to the canonical carnitine reaction. Reason: InterPro IPR000542 and the family evidence support carnitine O-palmitoyltransferase activity, GO:0004095. The independently demonstrated peptide-lysine succinyltransferase activity in PMID:29425493 is retained in its own molecular-function core, but is not assigned as a replacement supported by this InterPro mapping. No NEW annotation is added: GO:0106076 descends from the existing GO:0016746 assertion, and a redundant new annotation is unnecessary for representing the independently supported activity in the synthesis. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: InterPro:IPR000542 SUPPORTS TRANSFER IPR000542 supports the canonical carnitine acyl-transfer refinement only. PMID:29425493 independently supports the separate succinyltransferase core; that experiment is not attributed to InterPro. Proposed replacements: carnitine O-palmitoyltransferase activity |
| GO:0001666 response to hypoxia | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the rat-supported hypoxia response at its expression-response scope. Reason: The exact rat P32198 donor has an IEP annotation from PMID:33310031. Its abstract reports altered myocardial CPT1alpha expression in rats exposed to obesity and hypoxia, with PPAR-alpha agonist intervention. The current term explicitly includes gene-expression changes in response to reduced oxygen. Retain this qualified ortholog response without asserting that CPT1A is an oxygen sensor; full donor Methods were not recovered. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P32198 SUPPORTS TRANSFER Exact current donor records: PMID:33310031. The target decision retains the assay and access limits stated in the reason; no historical curation session is inferred. ensembl:ENSRNOP00000019652 SUPPORTS TRANSFER The literal current source and its biological scope are recorded in the evidence index; historical omitted fields remain omitted. Supporting Evidence: |
| GO:0001676 long-chain fatty acid metabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: Long-chain fatty-acid metabolism is the performed substrate pathway. Reason: The literal rat donor records and direct human carnitine/palmitoyl-CoA assays agree. CPT1A chemically converts a long-chain acyl-CoA into acylcarnitine, rather than merely accompanying fatty-acid metabolism. The existing donor transfer is compatible with the independently established human reaction. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P32198 SUPPORTS TRANSFER Exact current donor records: GO_REF:0000107, GO_REF:0000121, PMID:19302064, PMID:21990363, PMID:9461513. The target decision retains the assay and access limits stated in the reason; no historical curation session is inferred. ensembl:ENSRNOP00000019652 SUPPORTS TRANSFER The literal current source and its biological scope are recorded in the evidence index; historical omitted fields remain omitted. Supporting Evidence: file:human/CPT1A/CPT1A-source-evidence.yaml |
| GO:0006006 glucose metabolic process | IEA GO_REF:0000107 | UNDECIDED | Summary: The positive neurohepatic phenotype does not yet resolve the glucose-pathway participation asserted by this transfer. Reason: The rat donor is grounded in PMID:12754501: hypothalamic liver-type CPT1 inhibition reduces endogenous glucose production and food intake. This is genuine metabolic coupling, not a CPT1C misidentification. GO:0006006 describes chemical reactions and pathways involving glucose; the accessible abstract and original Figure 3 context do not resolve which glucose-pathway step CPT1A itself performs or how its lipid-metabolic action should be represented in that pathway. Full original Methods were not recovered. Retain uncertainty rather than infer either direct glucose metabolism from the physiological output or absence of a role. Row 28 asks the different, narrower question of maintaining intracellular glucose concentration and also has an unresolved historical mouse premise. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P32198 UNRESOLVED The literal donor mapping and positive experimental phenotype are verified as recorded in the evidence index. The target-level process interpretation remains unresolved for the specific reasons above; this does not assert that the donor result or historical curation is false. ensembl:ENSRNOP00000019652 UNRESOLVED The literal donor mapping and positive experimental phenotype are verified as recorded in the evidence index. The target-level process interpretation remains unresolved for the specific reasons above; this does not assert that the donor result or historical curation is false. Supporting Evidence: |
| GO:0006631 fatty acid metabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: The ortholog transfer of fatty-acid metabolism is biologically sound. Reason: The exact P32198 donor records include experimental fatty-acid oxidation evidence, and human CPT1A directly converts fatty acyl-CoA substrates. Retain this valid broad electronic pathway assertion alongside the more precise long-chain and shuttle annotations. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P32198 SUPPORTS TRANSFER Exact current donor records: GO_REF:0000033, PMID:24222496, PMID:30851372, PMID:31639005. The target decision retains the assay and access limits stated in the reason; no historical curation session is inferred. ensembl:ENSRNOP00000019652 SUPPORTS TRANSFER The literal current source and its biological scope are recorded in the evidence index; historical omitted fields remain omitted. Supporting Evidence: file:human/CPT1A/CPT1A-source-evidence.yaml |
| GO:0006635 fatty acid beta-oxidation | IEA GO_REF:0000120 | ACCEPT | Summary: CPT1A performs an entry reaction in the fatty-acid beta-oxidation pathway. Reason: CPT1A catalyzes acylcarnitine formation in the carnitine shuttle, supplying long-chain substrate for mitochondrial beta-oxidation. The current GO:0006635 definition explicitly mentions CoA addition, not the CPT1A carnitine-transfer reaction, so that clause alone is not the justification. Existing human pathway assertions, deficiency and reaction evidence, and the protected GO-CAM placement support participation in the overall mitochondrial pathway without assigning its repeated dehydrogenation or thiolysis reactions to CPT1A. Current ARBA00028692 branch 15 matches both target FunFams and Catarrhini. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00028692 SUPPORTS TRANSFER Current rule/reaction applicability is reconstructed from official target identifiers and taxonomy. It is not a replay of the historical electronic inference. UniProtKB:P32198 SUPPORTS TRANSFER Current rule/reaction applicability is reconstructed from official target identifiers and taxonomy. It is not a replay of the historical electronic inference. ensembl:ENSRNOP00000019652 SUPPORTS TRANSFER Current rule/reaction applicability is reconstructed from official target identifiers and taxonomy. It is not a replay of the historical electronic inference. UniPathway:UPA00659 SUPPORTS TRANSFER Current rule/reaction applicability is reconstructed from official target identifiers and taxonomy. It is not a replay of the historical electronic inference. |
| GO:0006641 triglyceride metabolic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the experimentally grounded coupling to triglyceride metabolism. Reason: Exact rat donor PMID:18349115 reports adenoviral CPT1a expression in primary rat hepatocytes and rats, increased fatty-acid oxidation and reduced triglyceride accumulation and secretion, with CPT2 and beta-galactosidase controls. The accessible abstract preserves these positive findings; full Methods remain unavailable. This supports non-core triglyceride metabolic coupling without claiming that CPT1A directly hydrolyzes or synthesizes triglyceride. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P32198 SUPPORTS TRANSFER Exact current donor records: PMID:18349115. The target decision retains the assay and access limits stated in the reason; no historical curation session is inferred. ensembl:ENSRNOP00000019652 SUPPORTS TRANSFER The literal current source and its biological scope are recorded in the evidence index; historical omitted fields remain omitted. Supporting Evidence: |
| GO:0007584 response to nutrient | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The nutrient-response annotation is supported by a specific rat expression experiment. Reason: The exact donor IEP points to PMID:33310031, which reports CPT1a expression changes under diet-induced obesity and hypoxia. GO:0007584 explicitly includes altered enzyme production or gene expression after a nutrient stimulus. Retain the existing transfer at this limited response scope rather than treating expression evidence as intrinsically invalid; no nutrient-receptor activity is inferred. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P32198 SUPPORTS TRANSFER Exact current donor records: PMID:33310031. The target decision retains the assay and access limits stated in the reason; no historical curation session is inferred. ensembl:ENSRNOP00000019652 SUPPORTS TRANSFER The literal current source and its biological scope are recorded in the evidence index; historical omitted fields remain omitted. Supporting Evidence: |
| GO:0009410 response to xenobiotic stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain xenobiotic-responsive CPT1A expression without assigning detoxification activity. Reason: Literal P32198 donor IEP records trace to PMID:19553925, PMID:31748600 and PMID:31953200. The actual full 31748600 rat Methods and Figure 3 results show alirocumab-associated restoration of hepatic CPT1 expression during alcohol exposure; the other accessible abstracts describe drug or herbal-treatment responses. This fits the response term's gene-expression scope, while the human transfer and incompletely accessed donor papers remain qualified. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P32198 SUPPORTS TRANSFER Exact current donor records: PMID:19553925, PMID:31748600, PMID:31953200. The target decision retains the assay and access limits stated in the reason; no historical curation session is inferred. ensembl:ENSRNOP00000019652 SUPPORTS TRANSFER The literal current source and its biological scope are recorded in the evidence index; historical omitted fields remain omitted. |
| GO:0009437 carnitine metabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: Carnitine metabolism is directly supported by the conserved enzymatic reaction. Reason: Exact rat donor records and human assays show transfer of a long-chain acyl group to carnitine. This performs the chemistry named by the term. It does not mean that CPT1A synthesizes free carnitine or supplies the inner-membrane exchange activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P32198 SUPPORTS TRANSFER Exact current donor records: GO_REF:0000033, GO_REF:0000120, GO_REF:0000121, PMID:12826662, PMID:21990363, PMID:24222496. The target decision retains the assay and access limits stated in the reason; no historical curation session is inferred. ensembl:ENSRNOP00000019652 SUPPORTS TRANSFER The literal current source and its biological scope are recorded in the evidence index; historical omitted fields remain omitted. Supporting Evidence: file:human/CPT1A/CPT1A-source-evidence.yaml |
| GO:0031667 response to nutrient levels | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Nutrient-level responses are retained as measured metabolic adaptations. Reason: The exact rat donor records trace to six diet/intervention studies. In the actual PMID:31639005 Methods and Results, high-fat-fed rats show changed hepatic Cpt-1alpha mRNA, measured with named qPCR primers and restored during myriocin treatment. Other selected abstracts report CPT1 expression changes after dietary interventions. These support the broad response definition, not a new sensing mechanism or an independently tested human response to each treatment. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P32198 SUPPORTS TRANSFER Exact current donor records: PMID:30851372, PMID:30868489, PMID:31639005, PMID:31901136, PMID:31930271, PMID:31953200. The target decision retains the assay and access limits stated in the reason; no historical curation session is inferred. ensembl:ENSRNOP00000019652 SUPPORTS TRANSFER The literal current source and its biological scope are recorded in the evidence index; historical omitted fields remain omitted. Supporting Evidence: |
| GO:0032000 positive regulation of fatty acid beta-oxidation | IEA GO_REF:0000107 | UNDECIDED | Summary: The measured increase in fatty-acid oxidation does not yet resolve a distinct regulatory annotation. Reason: The exact rat donor is grounded in PMID:19302064, whose abstract reports increased oleate beta-oxidation after expression of wild-type or malonyl-insensitive CPT1A in hepatocytes exposed to high glucose and insulin. This is positive control of pathway flux by changing CPT1A catalytic capacity and its susceptibility to inhibition. It does not by itself distinguish participation in the pathway from a regulatory mechanism represented by GO:0032000. The earlier rationale that any rate-controlling catalytic step establishes this regulation was too broad. Full original Methods were not recovered, so the source-specific regulatory interpretation remains unresolved rather than contradicted; neither the positive oxidation result nor the donor annotation is dismissed. The GO definition describes a change in rate or extent and does not itself require a noncatalytic mechanism; the uncertainty concerns annotation interpretation and mechanistic attribution in these particular assays. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P32198 UNRESOLVED The literal donor mapping and positive experimental phenotype are verified as recorded in the evidence index. The target-level process interpretation remains unresolved for the specific reasons above; this does not assert that the donor result or historical curation is false. ensembl:ENSRNOP00000019652 UNRESOLVED The literal donor mapping and positive experimental phenotype are verified as recorded in the evidence index. The target-level process interpretation remains unresolved for the specific reasons above; this does not assert that the donor result or historical curation is false. Supporting Evidence: |
| GO:0042755 eating behavior | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The eating-behavior transfer has genuine CPT1A donor evidence. Reason: The exact P32198 IMP record points to PMID:12754501. The original abstract and Figure 3 identify hypothalamic liver-type CPT1 suppression, associated with reduced food intake and hepatic glucose production. This is not disproved by a separate CPT1C feeding study. Retain the qualified rat-derived physiological role without claiming a primary human appetite receptor or full access to the original Methods. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P32198 SUPPORTS TRANSFER Exact current donor records: PMID:12754501. The target decision retains the assay and access limits stated in the reason; no historical curation session is inferred. ensembl:ENSRNOP00000019652 SUPPORTS TRANSFER The literal current source and its biological scope are recorded in the evidence index; historical omitted fields remain omitted. Supporting Evidence: |
| GO:0042802 identical protein binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive CPT1A self-association is supported by native and recombinant rat assays. Reason: PMID:19136561 directly examines rat liver mitochondrial CPT1A, full-length rat protein expressed in yeast and isolated TM2 constructs. BN-PAGE, cross-linking and analytical ultracentrifugation support oligomerization; the native preparations contain trimers and hexamers with preparation-dependent proportions. This supports identical-protein binding, but neither a homodimer-specific replacement nor a proven acylcarnitine-channel mechanism. The conserved human transfer remains distinct from a direct human oligomer measurement. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P32198 SUPPORTS TRANSFER Exact current donor records: PMID:19136561. The target decision retains the assay and access limits stated in the reason; no historical curation session is inferred. ensembl:ENSRNOP00000019652 SUPPORTS TRANSFER The literal current source and its biological scope are recorded in the evidence index; historical omitted fields remain omitted. Supporting Evidence: |
| GO:0043279 response to alkaloid | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the specific alkaloid-associated expression response. Reason: The exact donor IEP uses PMID:30868489, whose abstract reports restoration of hepatic CPT1A expression during berberine treatment of high-fat-fed rats. The response definition includes changes in expression. Full donor Methods were not recovered, so the retained ortholog assertion does not imply that CPT1A binds berberine or senses alkaloids directly. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P32198 SUPPORTS TRANSFER Exact current donor records: PMID:30868489. The target decision retains the assay and access limits stated in the reason; no historical curation session is inferred. ensembl:ENSRNOP00000019652 SUPPORTS TRANSFER The literal current source and its biological scope are recorded in the evidence index; historical omitted fields remain omitted. Supporting Evidence: |
| GO:0045471 response to ethanol | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the qualified ethanol-response transfer. Reason: The literal rat donor IEP is PMID:27939985. Its abstract reports ethanol, FXR and DHA interventions but does not expose the target-level CPT1 assay, so that original experimental curation is retained with an explicit access limit. Independently, the actual PMID:31748600 rat Results show alcohol-associated reduction of CPT1 mRNA. This supports a response context without asserting a direct ethanol receptor or silently replacing the original donor citation. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P32198 SUPPORTS TRANSFER Exact current donor records: PMID:27939985. The target decision retains the assay and access limits stated in the reason; no historical curation session is inferred. ensembl:ENSRNOP00000019652 SUPPORTS TRANSFER The literal current source and its biological scope are recorded in the evidence index; historical omitted fields remain omitted. |
| GO:0046320 regulation of fatty acid oxidation | IEA GO_REF:0000107 | UNDECIDED | Summary: The performed activity and flux assays leave the specific regulation-of-oxidation interpretation unresolved. Reason: Actual PMID:11988095 Methods identify sequence-verified full-length rat liver CPT1 expressed in INS1E cells. Increased CPT activity and palmitate oxidation, with etomoxir controls, are positive experimental results; the authors describe direct control of fatty-acid oxidation flux. These observations establish the catalytic entry step and its metabolic consequences, but do not resolve a regulatory mechanism distinct from increasing that step itself. PMID:19302064 corroborates flux changes, while its full Methods remain unavailable here. GO:0046320 is therefore UNDECIDED at this source-specific participation-versus-regulation boundary, not rejected because the assays are in rat cells or because positive flux control is absent. The GO definition describes a change in rate or extent and does not itself require a noncatalytic mechanism; the uncertainty concerns annotation interpretation and mechanistic attribution in these particular assays. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P32198 UNRESOLVED The literal donor mapping and positive experimental phenotype are verified as recorded in the evidence index. The target-level process interpretation remains unresolved for the specific reasons above; this does not assert that the donor result or historical curation is false. ensembl:ENSRNOP00000019652 UNRESOLVED The literal donor mapping and positive experimental phenotype are verified as recorded in the evidence index. The target-level process interpretation remains unresolved for the specific reasons above; this does not assert that the donor result or historical curation is false. |
| GO:0050796 regulation of insulin secretion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the experimentally supported, context-dependent effect on insulin secretion. Reason: Actual PMID:11988095 Methods and Results identify full-length rat liver CPT1 overexpression in INS1E cells, reduced secretion at high glucose, partial reversal after etomoxir preincubation and palmitate rescue. KCl responses and glucose utilization provide specificity controls. This is a positive metabolic contribution to secretory regulation in that system, not merely an unspecified downstream association or a universal inhibition of insulin secretion in humans. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P32198 SUPPORTS TRANSFER Exact current donor records: PMID:11988095. The target decision retains the assay and access limits stated in the reason; no historical curation session is inferred. ensembl:ENSRNOP00000019652 SUPPORTS TRANSFER The literal current source and its biological scope are recorded in the evidence index; historical omitted fields remain omitted. Supporting Evidence: |
| GO:0071398 cellular response to fatty acid | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Fatty-acid-responsive CPT1A expression is directly observed in the rat donor system. Reason: PMID:19332540 uses rat H4IIEC3 hepatocytes. Actual Methods and Figure 9 results show that palmitate, unlike oleate under the tested conditions, increases Cpt1a mRNA; etomoxir affects the associated ROS response. This fits the term's expression-response definition. The transfer does not assign CPT1A a fatty-acid receptor role or prove equivalent human responses to every fatty acid. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P32198 SUPPORTS TRANSFER Exact current donor records: PMID:19332540. The target decision retains the assay and access limits stated in the reason; no historical curation session is inferred. ensembl:ENSRNOP00000019652 SUPPORTS TRANSFER The literal current source and its biological scope are recorded in the evidence index; historical omitted fields remain omitted. Supporting Evidence: |
| GO:0097421 liver regeneration | IEA GO_REF:0000107 | UNDECIDED | Summary: The particular liver-regeneration premise remains unresolved. Reason: The exact rat donor IEP points to PMID:31953200, and its abstract reports liver lipid responses, Cpt1A expression and activity after Polygoni Multiflori treatment. These are genuine positive metabolic observations, but the available abstract does not resolve the regrowth of lost or destroyed liver required by GO:0097421. Full original Methods were not recovered. Preserve the source and uncertainty rather than claiming that CPT1A cannot contribute to liver regeneration. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P32198 UNRESOLVED The donor IEP is literal and positive, but the available source does not resolve liver regrowth rather than lipid responses; full Methods remain inaccessible. ensembl:ENSRNOP00000019652 UNRESOLVED The donor IEP is literal and positive, but the available source does not resolve liver regrowth rather than lipid responses; full Methods remain inaccessible. Supporting Evidence: |
| GO:1904772 response to tetrachloromethane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the tetrachloromethane-associated metabolic response. Reason: The exact rat donor IEP is PMID:31918260. Its abstract describes carbon-tetrachloride liver injury, glycyrrhizic-acid interventions and restoration of CPT1a expression with lipid-metabolic changes. This is compatible with the response term, whose definition includes expression changes. Full Methods remain unavailable; no direct chemical sensing or detoxification reaction by CPT1A is asserted. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P32198 SUPPORTS TRANSFER Exact current donor records: PMID:31918260. The target decision retains the assay and access limits stated in the reason; no historical curation session is inferred. ensembl:ENSRNOP00000019652 SUPPORTS TRANSFER The literal current source and its biological scope are recorded in the evidence index; historical omitted fields remain omitted. Supporting Evidence: |
| GO:0001678 intracellular glucose homeostasis | ISS GO_REF:0000024 | UNDECIDED | Summary: Intracellular glucose homeostasis is more specific than the currently resolved donor evidence. Reason: The historical mouse source MGI:MGI:1098296 is retained exactly. Current complete mouse UniProt and MGI annotation captures do not recover this exact term, so they cannot reconstruct the historical premise. Human GO-CAM 69ea894900000564 does preserve the same ISS context, placing CPT1A activity in beta-oxidation and then intracellular glucose homeostasis; it does not supply a separate direct experiment. Known effects on hepatic glucose production or whole-body glucose balance do not by themselves establish maintenance of intracellular glucose concentration. This is unresolved source and biological specificity, not a claim that the function is absent or that the curated model or mouse record is wrong. Propagation Review Root cause: UNRESOLVED Sources checked: MGI:MGI:1098296 SOURCE STALE OR MISSING The complete current mouse captures do not recover this term; historical experimental grounding remains unresolved, not disproved. Supporting Evidence: file:human/CPT1A/CPT1A-source-evidence.yaml |
| GO:0006635 fatty acid beta-oxidation | ISS GO_REF:0000024 | ACCEPT | Summary: The mouse-derived beta-oxidation assertion agrees with the human performed pathway step. Reason: The current mouse records available for this term are electronic rather than a reconstruction of the historical ISS source experiment. That limitation is explicit in the source assessment. Independently, human CPT1A catalysis and deficiency studies establish participation in the overall beta-oxidation pathway; the assertion is retained without claiming a newly verified direct mouse experiment. Propagation Review Root cause: NO FAILURE CORE Sources checked: MGI:MGI:1098296 SOURCE WEAK OR INFERRED Current mouse matching records are electronic; independent human chemistry supports pathway participation without reconstructing a missing historical mouse experiment. Supporting Evidence: file:human/CPT1A/CPT1A-source-evidence.yaml |
| GO:0006853 carnitine shuttle | TAS Reactome:R-HSA-200425 | ACCEPT | Summary: Reactome explicitly places the CPT1A catalytic step within the carnitine shuttle. Reason: The actual pathway R-HSA-200425 contains reaction R-HSA-200406, whose catalyst activity 201041 resolves through protein entity 400161 to UniProt P50416. CPT1A performs acylcarnitine formation, while the translocase and CPT2 perform distinct shuttle steps. This is an exact target participation path, not merely membership in a broad metabolic pathway. Supporting Evidence: Reactome:R-HSA-200425 carnitine palmitoyltransferase I (CPT-I) localized in the mitochondrial outer membrane Reactome:R-HSA-200406 file:human/CPT1A/CPT1A-source-evidence.yaml |
| GO:0004095 carnitine O-palmitoyltransferase activity | EXP PMID:14517221 Functional and structural basis of carnitine palmitoyltransf... | ACCEPT | Summary: The original study directly measures the human canonical reaction. Reason: Full original PMID:14517221 Methods and Results specify full-length human CPT1A expressed in yeast and assays in mitochondrial preparations with carnitine and palmitoyl-CoA. Wild-type kinetics and malonyl-CoA sensitivity support the activity. Its structure-function interpretation is a comparative model, not an experimental structure of human CPT1A, and it does not establish equivalent activity of both current human products. Supporting Evidence: PMID:14517221 Carnitine palmitoyltransferase 1A (CPT1A) is the key regulatory enzyme of hepatic long-chain fatty acid beta-oxidation. |
| GO:0005739 mitochondrion | IDA GO_REF:0000052 | ACCEPT | Summary: Retain the mitochondrial location at the HPA assay's actual resolution. Reason: The actual Human Protein Atlas target record and original immunofluorescence-derived GOA source support mitochondria. The broader compartment is appropriate for the assay resolution and remains compatible with the independently supported outer membrane. No ordinary source qualifier or inferred high-resolution topology is used to overrule the positive location. Supporting Evidence: file:human/CPT1A/CPT1A-source-evidence.yaml |
| GO:0004095 carnitine O-palmitoyltransferase activity | EXP PMID:16651524 The brain-specific carnitine palmitoyltransferase-1c regulat... | ACCEPT | Summary: The CPT1C-focused paper contains a direct positive CPT1A control assay. Reason: The recovered full PMID:16651524 Results, Figure 1, Table 1 and Methods measure CPT1A-dependent acylcarnitine formation against H473A and CPT1C controls in transfected HEK293T preparations. The activity-vector insert species is not explicitly resolved, while separate immunoblot Methods mention mouse constructs; the human host alone cannot establish insert species. Retain the positive curated activity, independently established for human CPT1A by other papers, without a wrong-paralog allegation. Supporting Evidence: PMID:16651524 CPT1a and CPT1b catalyze acyl transfer from various fatty acyl-CoAs to carnitine |
| GO:0005741 mitochondrial outer membrane | EXP PMID:11350182 Molecular and enzymatic characterization of a unique carniti... | ACCEPT | Summary: Retain the supported outer-membrane location with the original paper's access limit. Reason: The complete PMID:11350182 abstract reports preserved mitochondrial targeting of the inactive G710E variant. Full original Methods were not recovered, so their specific localization protocol is not invented. The independently established CPT1A outer-membrane context and experimental curator judgment support retaining this annotation. Supporting Evidence: PMID:11350182 alters neither mitochondrial targeting nor stability of the CPT1A protein. |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: Original MitoCoP target data support mitochondrial localization at protein-group resolution. Reason: The authenticated workbook has CPT1A group 4917 in both the all-protein and MitoCoP sheets. P50416 and P50416-2 are grouped, rather than resolved individually. Subtractive and spatial data support the mitochondrial assignment. The blank membrane category, only one valid carbonate ratio and inherited outer-membrane annotation column do not independently establish integral topology or isoform-specific outer-membrane localization. Supporting Evidence: |
| GO:0030674 protein-macromolecule adaptor activity | IDA PMID:38016475 CPT1A induction following epigenetic perturbation promotes M... | ACCEPT | Summary: Retain the defined CPT1A adaptor role in bringing ZDHHC4 to MAVS. Reason: The complete PMID:38016475 abstract explicitly reports CPT1A recruitment of ER-localized ZDHHC4 for MAVS Cys79 palmitoylation. The protected human GO-CAM 65bc474400000029 independently records this curated IDA adaptor activity, its two molecular inputs and its link to ZDHHC4 activity. Full original Methods were not recovered; no unverified H473A result, native binary interface or proof of catalytic independence is added. The reported recruitment role is a distinct molecular function rather than generic binding. Supporting Evidence: PMID:38016475 CPT1A recruits the endoplasmic reticulum-localized ZDHHC4 to catalyze MAVS Cys79-palmitoylation |
| GO:0045089 positive regulation of innate immune response | IDA PMID:38016475 CPT1A induction following epigenetic perturbation promotes M... | ACCEPT | Summary: The defined adaptor activity positively regulates the MAVS-dependent innate response. Reason: PMID:38016475 reports sustained double-stranded-RNA-activated type I interferon responses through ZDHHC4 recruitment and MAVS stabilization; the existing human GO-CAM explicitly places the CPT1A adaptor activity in GO:0045089. Retain this curated positive role with the abstract-only original access boundary. CPT1A is not asserted to catalyze MAVS palmitoylation itself, to govern all innate immunity or to perform every antitumor effect. Supporting Evidence: |
| GO:0004095 carnitine O-palmitoyltransferase activity | IMP PMID:14517221 Functional and structural basis of carnitine palmitoyltransf... | ACCEPT | Summary: Human CPT1A variants directly perturb the canonical enzymatic activity. Reason: Actual PMID:14517221 yeast-expression assays compare full-length human wild-type and disease variants. Loss or alteration of activity supports the IMP assertion in addition to the direct wild-type assay. Mutant activity, abundance and structural-model interpretation must be distinguished; this source is not an all-product functional comparison. Supporting Evidence: |
| GO:0004095 carnitine O-palmitoyltransferase activity | IMP PMID:9691089 Molecular basis of hepatic carnitine palmitoyltransferase I ... | ACCEPT | Summary: The D454G human variant supports the catalytic activity assertion. Reason: The complete PMID:9691089 abstract reports a human case, reduced patient-fibroblast protein and about 2 percent wild-type activity after yeast expression. Full original Methods were not recovered. Retain the experimentally curated activity with this clear positive evidence, without treating the measured defect as purified intrinsic kinetics independent of protein abundance. Supporting Evidence: PMID:9691089 The expressed mutant CPT IA displayed only 2% of the activity of the expressed wild-type CPT IA |
| GO:0005741 mitochondrial outer membrane | IMP PMID:14517221 Functional and structural basis of carnitine palmitoyltransf... | ACCEPT | Summary: Human CPT1A mutational studies support its outer-membrane context. Reason: The original PMID:14517221 examines human protein in yeast mitochondrial preparations, including fractionation and proteolysis in intact or solubilized mitochondria. These experiments support the membrane-associated context of the functional enzyme and variants. The source remains an IMP annotation and is not recast as a native human-cell high-resolution topology experiment. Supporting Evidence: |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MODIFY | Summary: Refine broad membrane to mitochondrial outer membrane using independent target evidence. Reason: PMID:19946888 reports a human NK-cell membrane proteome, but its target table was not recovered and the selected cache is abstract-only. The positive membrane assertion is retained with curator deference. Independently, the established CPT1A topology and human enzyme studies support mitochondrial outer membrane, GO:0005741, as a more precise target-level replacement. This refinement uses that additional evidence; it does not claim that the NK-cell proteomic assay resolved outer versus inner membrane, an individual isoform, or an NK-specific immune function. Proposed replacements: mitochondrial outer membrane |
| GO:0004095 carnitine O-palmitoyltransferase activity | IDA PMID:7892212 Human liver mitochondrial carnitine palmitoyltransferase I: ... | ACCEPT | Summary: The foundational human study includes a direct fibroblast CPT assay. Reason: The original five-page PMID:7892212 report combines human liver cDNA cloning with endogenous human fibroblast homogenate assays retaining intact mitochondria, including carnitine kinetics, malonyl sensitivity and etomoxir labeling. It establishes genuine human activity; it should not be described as an assay of recombinant cloned human enzyme in this paper. Supporting Evidence: PMID:7892212 liver and fibroblasts express the same isoform of mitochondrial CPT I |
| GO:0030855 epithelial cell differentiation | IEP PMID:21492153 Analysis of proteomic changes induced upon cellular differen... | UNDECIDED | Summary: CPT1A expression changes during epithelial differentiation, but its functional contribution remains unclear. Reason: Actual original PMID:21492153 Methods and Results compare Caco-2 cells at day 0 and day 17 with differentiation markers and proteomics. Table 1 identifies P50416 and a 4.02-fold increase; CPT1A was not among the seven selected proteins independently validated by immunoblot or qPCR. This is genuine target expression evidence. The read passages do not resolve whether CPT1A performs part of the acquisition of epithelial specialization, but neither do they disprove a metabolic contribution. Uncertainty concerns participation, not a claim that no full text was accessed. Supporting Evidence: |
| GO:0005741 mitochondrial outer membrane | TAS Reactome:R-HSA-200406 | ACCEPT | Summary: The Reactome catalyst entity explicitly places human CPT1A in the outer membrane. Reason: R-HSA-200406 catalyst 201041 uses protein entity 400161, which resolves to P50416 and GO:0005741. The reaction's multiple substrate compartments must not be assigned wholesale to the protein. Its narrative first sentence says inner membrane, conflicting with its structured catalyst location and primary evidence; that wording error is documented while retaining the supported outer-membrane assertion. Supporting Evidence: Reactome:R-HSA-200406 Reactome:R-HSA-200425 file:human/CPT1A/CPT1A-source-evidence.yaml |
| GO:0001676 long-chain fatty acid metabolic process | IDA PMID:11350182 Molecular and enzymatic characterization of a unique carniti... | ACCEPT | Summary: The human deficiency study supports long-chain fatty-acid metabolism. Reason: PMID:11350182 directly concerns CPT1A deficiency and an inactive G710E enzyme with preserved mitochondrial targeting. The accessible abstract and independently established long-chain reaction support the existing experimental process annotation. Full original Methods remain unavailable, so no particular substrate series or quantitative flux assay is claimed from this source. Supporting Evidence: |
| GO:0004095 carnitine O-palmitoyltransferase activity | IDA PMID:11350182 Molecular and enzymatic characterization of a unique carniti... | ACCEPT | Summary: Retain the experimental catalytic assertion supported by the inactive human G710E variant. Reason: The complete PMID:11350182 abstract explicitly reports an inactive variant after fibroblast and yeast studies. Together with independent direct human CPT1A enzymology, this supports the curated activity assertion despite unavailable full original Methods. Original evidence and source fields are preserved. Supporting Evidence: |
| GO:0005739 mitochondrion | IDA PMID:11350182 Molecular and enzymatic characterization of a unique carniti... | ACCEPT | Summary: The paper directly supports mitochondrial targeting at its reported resolution. Reason: The PMID:11350182 abstract states that G710E does not alter mitochondrial targeting or stability. Retain this positive mitochondrial location with full-Methods access limits rather than inventing a finer assay. More specific outer-membrane annotations are independently supported elsewhere. Supporting Evidence: |
| GO:0005741 mitochondrial outer membrane | ISS GO_REF:0000024 | ACCEPT | Summary: The rat-derived outer-membrane assignment agrees with independently established human localization. Reason: The literal P32198 donor source and its current records are retained in the evidence index. Rat full-length mitochondrial and transmembrane studies provide consistent context, while the human CPT1A literature independently supports the outer membrane. The transfer does not demonstrate identical oligomeric stoichiometry or activity of each human product. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P32198 SUPPORTS TRANSFER Exact current donor records: GO_REF:0000120, GO_REF:0000121, PMID:11087756, PMID:15247243, PMID:16908527, PMID:18192268, PMID:19136561, PMID:21622568, PMID:9169604. The target decision retains the assay and access limits stated in the reason; no historical curation session is inferred. Supporting Evidence: file:human/CPT1A/CPT1A-source-evidence.yaml |
| GO:0009437 carnitine metabolic process | IDA PMID:11350182 Molecular and enzymatic characterization of a unique carniti... | ACCEPT | Summary: The catalytic reaction directly uses and modifies carnitine. Reason: The G710E study's positive wild-type context and the independently measured human acyl-transfer reaction support carnitine metabolism. Full PMID:11350182 Methods were not recovered, so the original experimental curator's assignment is retained without inventing an additional carnitine-biosynthetic role. Supporting Evidence: |
| GO:0004095 carnitine O-palmitoyltransferase activity | TAS PMID:7892212 Human liver mitochondrial carnitine palmitoyltransferase I: ... | ACCEPT | Summary: The original human CPT1 study supports the canonical activity. Reason: PMID:7892212 directly links the human liver sequence to the fibroblast mitochondrial enzyme and measures its catalytic properties. Retain the source's TAS assertion alongside the separate IDA row; same-term source-specific assertions are not redundant NEW annotations. Supporting Evidence: |
| GO:0005739 mitochondrion | TAS PMID:7892212 Human liver mitochondrial carnitine palmitoyltransferase I: ... | MODIFY | Summary: Refine the broad foundational mitochondrial location using the established outer-membrane context. Reason: The original human PMID:7892212 study supports mitochondrial CPT1 and predicts membrane-spanning segments. Later human protein and topology evidence resolve the outer membrane. This holistic target refinement does not claim that the 1995 paper itself performed a modern membrane-topology assay. Proposed replacements: mitochondrial outer membrane Supporting Evidence: |
| GO:0006635 fatty acid beta-oxidation | TAS PMID:7892212 Human liver mitochondrial carnitine palmitoyltransferase I: ... | ACCEPT | Summary: The original human enzymology supports entry into fatty-acid beta-oxidation. Reason: CPT1A catalyzes acylcarnitine formation in the transport system supplying mitochondrial long-chain fatty acids. The source's beta-oxidation assertion fits the current pathway definition and the human biochemical evidence. It does not assign the downstream repeated oxidation-cycle reactions to CPT1A. Supporting Evidence: |
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Download this section (compressed HTML)Q: Do the 773- and 756-residue human products differ in canonical catalysis, lysine succinylation or MAVS-associated recruitment? The human isoform-2 N-terminal peptide does not establish full-length equivalence.
Q: Which endogenous CPT1A-dependent succinylation sites are direct enzyme substrates, and how do their physiological concentrations and locations constrain the purified ENO1 reaction?
Experiment: Compare matched expression, mitochondrial topology and canonical kinetics of both full-length human products, then test ENO1 succinylation and ZDHHC4/MAVS recruitment in the same controlled system; separate abundance or targeting effects from intrinsic activity differences.
Hypothesis: The two full-length human products may differ in one or more reported activities.
Type: Product-resolved biochemical and cellular complementation assays
Experiment: Combine endogenous CPT1A depletion and rescue with site-resolved succinylation measurements and purified candidate-substrate assays over measured cellular succinyl-CoA concentrations, including no-enzyme and no-donor controls.
Hypothesis: Only a subset of CPT1A-dependent cellular succinylation sites are direct substrates under physiological conditions.
Type: Quantitative proteomics and controlled enzyme assays
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