Crot encodes peroxisomal carnitine O-octanoyltransferase (COT), a member of the carnitine/choline acetyltransferase family that is imported into peroxisomes by a C-terminal Ala-His-Leu targeting signal. COT reversibly transfers acyl groups between coenzyme A and L-carnitine; it acts on saturated acyl-CoAs from C2 to C20 with an optimum at C6-C10, and also on branched-chain intermediates such as 4,8-dimethylnonanoyl-CoA from pristanic acid oxidation. By converting the medium-chain and branched-chain acyl-CoA products of peroxisomal beta-oxidation into acylcarnitines, it allows these chain-shortened fatty acids to leave the peroxisome for complete oxidation in mitochondria, and it regenerates free CoA inside the organelle. COT is abundant in liver, is induced by peroxisome proliferators, and is inhibited by malonyl-CoA and the drug etomoxir through two active-site-proximal histidines (His131 and His340).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005777 peroxisome | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN001097142 (CROT clade), with rat Crot itself (RGD:70908), mouse Crot and human CROT among the seed members. Rat COT was found in liver peroxisomes and carries a C-terminal peroxisomal targeting sequence. Reason: Previously KEEP_AS_NON_CORE. Peroxisomal localization is the defining location of Crot (C-terminal AHL peroxisomal targeting signal; enzyme purified from rat liver peroxisomes), and the peroxisome is where it converts medium-chain and branched-chain beta-oxidation products to acylcarnitines for export, so it is accepted as the core location. Supporting Evidence: UniProtKB:P11466 SUBCELLULAR LOCATION: Peroxisome PMID:6630173 COT was found in peroxisomes and the soluble compartment but not in mitochondria PMID:7495866 a C-terminal peroxisomal targeting sequence (Ala-His-Leu) |
| GO:0008458 carnitine O-octanoyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Crot's peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation supports retaining carnitine O-octanoyltransferase activity as a direct annotation (IBA, GO_REF:0000033). Reason: carnitine O-octanoyltransferase activity directly matches Crot's documented role in peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation. Supporting Evidence: UniProtKB:P11466 FUNCTION: Beta-oxidation of fatty acids. The highest activity concerns the C6 to C10 chain length substrate. file:rat/Crot/Crot-deep-research-falcon.md CROT is a **peroxisomal carnitine acyltransferase** that catalyzes a reversible acylโtransfer reaction: **Lโcarnitine + acylโCoA โ acylโLโcarnitine + CoASH**. |
| GO:0005777 peroxisome | IEA GO_REF:0000120 | ACCEPT | Summary: ARBA/SubCell-based peroxisome assignment, consistent with direct localization of rat COT to peroxisomes and its C-terminal peroxisomal targeting signal. Reason: Previously KEEP_AS_NON_CORE. Peroxisomal localization is the defining location of Crot (C-terminal AHL peroxisomal targeting signal; enzyme purified from rat liver peroxisomes), and the peroxisome is where it converts medium-chain and branched-chain beta-oxidation products to acylcarnitines for export, so it is accepted as the core location. Supporting Evidence: UniProtKB:P11466 SUBCELLULAR LOCATION: Peroxisome PMID:6630173 COT was found in peroxisomes and the soluble compartment but not in mitochondria PMID:7495866 a C-terminal peroxisomal targeting sequence (Ala-His-Leu) |
| GO:0008458 carnitine O-octanoyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Crot's peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation supports retaining carnitine O-octanoyltransferase activity as a direct annotation (IEA, GO_REF:0000120). Reason: carnitine O-octanoyltransferase activity directly matches Crot's documented role in peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation. Supporting Evidence: UniProtKB:P11466 FUNCTION: Beta-oxidation of fatty acids. The highest activity concerns the C6 to C10 chain length substrate. file:rat/Crot/Crot-deep-research-falcon.md Across sources, CROT is described as preferring **mediumโchain acylโCoAs** |
| GO:0015908 fatty acid transport | IEA GO_REF:0000117 | MODIFY | Summary: fatty acid transport captures part of Crot biology, but a more specific replacement better represents the direct role (IEA, GO_REF:0000117). Reason: fatty acid transport is directionally related to Crot but should be replaced by the more specific term(s): medium-chain fatty acid transport. Proposed replacements: medium-chain fatty acid transport Supporting Evidence: UniProtKB:P11466 FUNCTION: Beta-oxidation of fatty acids. The highest activity concerns the C6 to C10 chain length substrate. file:rat/Crot/Crot-deep-research-falcon.md CROT contributes by converting these mediumโchain acylโCoAs to **acylcarnitines**, which can be transported out of peroxisomes and then further metabolized (including by mitochondria). |
| GO:0016746 acyltransferase activity | IEA GO_REF:0000002 | MODIFY | Summary: acyltransferase activity captures part of Crot biology, but a more specific replacement better represents the direct role (IEA, GO_REF:0000002). Reason: acyltransferase activity is directionally related to Crot but should be replaced by the more specific term(s): carnitine O-octanoyltransferase activity. Proposed replacements: carnitine O-octanoyltransferase activity Supporting Evidence: UniProtKB:P11466 FUNCTION: Beta-oxidation of fatty acids. The highest activity concerns the C6 to C10 chain length substrate. file:rat/Crot/Crot-deep-research-falcon.md It catalyzes the **reversible transfer** between **L-carnitine + acyl-CoA โ acyl-L-carnitine + CoASH**. |
| GO:0006635 fatty acid beta-oxidation | IEA GO_REF:0000041 | ACCEPT | Summary: Crot's peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation supports retaining fatty acid beta-oxidation as a direct annotation (IEA, GO_REF:0000041). Reason: fatty acid beta-oxidation is a direct process-level consequence of Crot's documented role in peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation. Supporting Evidence: UniProtKB:P11466 FUNCTION: Beta-oxidation of fatty acids. The highest activity concerns the C6 to C10 chain length substrate. file:rat/Crot/Crot-deep-research-falcon.md Core pathway role is export of **peroxisomal ฮฒ-oxidation products** as **acylcarnitines** for downstream mitochondrial oxidation. |
| GO:0008458 carnitine O-octanoyltransferase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Crot's peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation supports retaining carnitine O-octanoyltransferase activity as a direct annotation (ISS, GO_REF:0000024). Reason: carnitine O-octanoyltransferase activity directly matches Crot's documented role in peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation. Supporting Evidence: UniProtKB:P11466 FUNCTION: Beta-oxidation of fatty acids. The highest activity concerns the C6 to C10 chain length substrate. file:rat/Crot/Crot-deep-research-falcon.md This chemistry is central to **acylcarnitine formation**, which is widely used by cells to move (or buffer) acyl groups across compartment boundaries where **acylโCoAs themselves are poorly membraneโpermeable**. |
| GO:0006631 fatty acid metabolic process | ISS GO_REF:0000024 | ACCEPT | Summary: Crot's peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation supports retaining fatty acid metabolic process as a direct annotation (ISS, GO_REF:0000024). Reason: fatty acid metabolic process is a direct process-level consequence of Crot's documented role in peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation. Supporting Evidence: UniProtKB:P11466 FUNCTION: Beta-oxidation of fatty acids. The highest activity concerns the C6 to C10 chain length substrate. |
| GO:0006631 fatty acid metabolic process | ISO GO_REF:0000121 | ACCEPT | Summary: Crot's peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation supports retaining fatty acid metabolic process as a direct annotation (ISO, GO_REF:0000121). Reason: fatty acid metabolic process is a direct process-level consequence of Crot's documented role in peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation. Supporting Evidence: UniProtKB:P11466 FUNCTION: Beta-oxidation of fatty acids. The highest activity concerns the C6 to C10 chain length substrate. |
| GO:0009437 carnitine metabolic process | ISS GO_REF:0000024 | ACCEPT | Summary: Crot's peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation supports retaining carnitine metabolic process as a direct annotation (ISS, GO_REF:0000024). Reason: carnitine metabolic process is a direct process-level consequence of Crot's documented role in peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation. Supporting Evidence: UniProtKB:P11466 Reaction=octanoyl-CoA + (R)-carnitine = O-octanoyl-(R)-carnitine + CoA; |
| GO:0009437 carnitine metabolic process | ISO GO_REF:0000121 | ACCEPT | Summary: Crot's peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation supports retaining carnitine metabolic process as a direct annotation (ISO, GO_REF:0000121). Reason: carnitine metabolic process is a direct process-level consequence of Crot's documented role in peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation. Supporting Evidence: UniProtKB:P11466 Reaction=octanoyl-CoA + (R)-carnitine = O-octanoyl-(R)-carnitine + CoA; |
| GO:0015936 coenzyme A metabolic process | ISS GO_REF:0000024 | ACCEPT | Summary: Crot's peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation supports retaining coenzyme A metabolic process as a direct annotation (ISS, GO_REF:0000024). Reason: coenzyme A metabolic process is a direct process-level consequence of Crot's documented role in peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation. Supporting Evidence: UniProtKB:P11466 Reaction=octanoyl-CoA + (R)-carnitine = O-octanoyl-(R)-carnitine + CoA; |
| GO:0015936 coenzyme A metabolic process | ISO GO_REF:0000121 | ACCEPT | Summary: Crot's peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation supports retaining coenzyme A metabolic process as a direct annotation (ISO, GO_REF:0000121). Reason: coenzyme A metabolic process is a direct process-level consequence of Crot's documented role in peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation. Supporting Evidence: UniProtKB:P11466 Reaction=octanoyl-CoA + (R)-carnitine = O-octanoyl-(R)-carnitine + CoA; |
| GO:0006091 generation of precursor metabolites and energy | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: generation of precursor metabolites and energy is retained as contextual support for Crot, but it is not the core function (ISO, GO_REF:0000121). Reason: generation of precursor metabolites and energy is biologically related to Crot, but it is broader, downstream, or regulatory context relative to peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation. Supporting Evidence: UniProtKB:P11466 FUNCTION: Beta-oxidation of fatty acids. The highest activity concerns the C6 to C10 chain length substrate. |
| GO:0006091 generation of precursor metabolites and energy | ISS PMID:10486279 Molecular cloning and expression of human carnitine octanoyl... | KEEP AS NON CORE | Summary: generation of precursor metabolites and energy is retained as contextual support for Crot, but it is not the core function (ISS, PMID:10486279). Reason: generation of precursor metabolites and energy is biologically related to Crot, but it is broader, downstream, or regulatory context relative to peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation. Supporting Evidence: PMID:10486279 To study the putative role of human carnitine octanoyltransferase (COT) in the beta-oxidation of branched-chain fatty acids, we identified and cloned the cDNA encoding human COT and expressed it in the yeast Saccharomyces cerevisiae. |
| GO:0008458 carnitine O-octanoyltransferase activity | ISO GO_REF:0000121 | ACCEPT | Summary: Crot's peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation supports retaining carnitine O-octanoyltransferase activity as a direct annotation (ISO, GO_REF:0000121). Reason: carnitine O-octanoyltransferase activity directly matches Crot's documented role in peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation. Supporting Evidence: UniProtKB:P11466 FUNCTION: Beta-oxidation of fatty acids. The highest activity concerns the C6 to C10 chain length substrate. |
| GO:0051791 medium-chain fatty acid metabolic process | ISO GO_REF:0000121 | ACCEPT | Summary: Crot's peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation supports retaining medium-chain fatty acid metabolic process as a direct annotation (ISO, GO_REF:0000121). Reason: medium-chain fatty acid metabolic process is a direct process-level consequence of Crot's documented role in peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation. Supporting Evidence: UniProtKB:P11466 FUNCTION: Beta-oxidation of fatty acids. The highest activity concerns the C6 to C10 chain length substrate. file:rat/Crot/Crot-deep-research-falcon.md CROT has also been implicated in handling **branchedโchain ฮฒโoxidation products**, including conversion of **4,8โdimethylnonanoylโCoA (DMNโCoA)** to a carnitine ester for downstream oxidation. |
| GO:0051791 medium-chain fatty acid metabolic process | ISS PMID:10486279 Molecular cloning and expression of human carnitine octanoyl... | ACCEPT | Summary: Crot's peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation supports retaining medium-chain fatty acid metabolic process as a direct annotation (ISS, PMID:10486279). Reason: medium-chain fatty acid metabolic process is a direct process-level consequence of Crot's documented role in peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation. Supporting Evidence: PMID:10486279 To study the putative role of human carnitine octanoyltransferase (COT) in the beta-oxidation of branched-chain fatty acids, we identified and cloned the cDNA encoding human COT and expressed it in the yeast Saccharomyces cerevisiae. |
| GO:0005777 peroxisome | ISO GO_REF:0000121 | ACCEPT | Summary: ISO from mouse Crot (MGI:1921364); peroxisomal localization of COT is conserved and directly shown for the rat enzyme. Reason: Previously KEEP_AS_NON_CORE. Peroxisomal localization is the defining location of Crot (C-terminal AHL peroxisomal targeting signal; enzyme purified from rat liver peroxisomes), and the peroxisome is where it converts medium-chain and branched-chain beta-oxidation products to acylcarnitines for export, so it is accepted as the core location. Propagation Review Root cause: NO FAILURE CORE Sources checked: MGI:MGI:1921364 ยท Crot SUPPORTS TRANSFER Mouse Crot donor; peroxisomal localization is conserved and is independently shown for rat COT (PMID:6630173). Supporting Evidence: UniProtKB:P11466 SUBCELLULAR LOCATION: Peroxisome PMID:6630173 COT was found in peroxisomes and the soluble compartment but not in mitochondria |
| GO:0006635 fatty acid beta-oxidation | ISO GO_REF:0000121 | ACCEPT | Summary: Crot's peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation supports retaining fatty acid beta-oxidation as a direct annotation (ISO, GO_REF:0000121). Reason: fatty acid beta-oxidation is a direct process-level consequence of Crot's documented role in peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation. Supporting Evidence: UniProtKB:P11466 FUNCTION: Beta-oxidation of fatty acids. The highest activity concerns the C6 to C10 chain length substrate. |
| GO:0005777 peroxisome | IDA PMID:6630173 Purification and properties of carnitine octanoyltransferase... | ACCEPT | Summary: IDA from Miyazawa et al. 1983 (PMID:6630173), who purified COT from liver of di(2-ethylhexyl)phthalate-treated rats and localized it to peroxisomes and the soluble compartment, not mitochondria. The soluble fraction may reflect leakage from fragile peroxisomes during fractionation. Reason: Previously KEEP_AS_NON_CORE. Peroxisomal localization is the defining location of Crot (C-terminal AHL peroxisomal targeting signal; enzyme purified from rat liver peroxisomes), and the peroxisome is where it converts medium-chain and branched-chain beta-oxidation products to acylcarnitines for export, so it is accepted as the core location. Supporting Evidence: PMID:6630173 COT was found in peroxisomes and the soluble compartment but not in mitochondria PMID:7495866 a C-terminal peroxisomal targeting sequence (Ala-His-Leu) |
| GO:0008458 carnitine O-octanoyltransferase activity | IDA PMID:11023836 Inhibition by etomoxir of rat liver carnitine octanoyltransf... | ACCEPT | Summary: Crot's peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation supports retaining carnitine O-octanoyltransferase activity as a direct annotation (IDA, PMID:11023836). Reason: Recombinant rat COT expressed in yeast (which lacks endogenous COT) was active with carnitine and decanoyl-CoA, direct evidence for the core activity of the rat enzyme. Supporting Evidence: PMID:11023836 The recombinant mutated enzymes showed activity towards both carnitine and decanoyl-CoA in the same range as the wild type. UniProtKB:P11466 Reaction=octanoyl-CoA + (R)-carnitine = O-octanoyl-(R)-carnitine + CoA; |
| GO:0009410 response to xenobiotic stimulus | IDA PMID:11023836 Inhibition by etomoxir of rat liver carnitine octanoyltransf... | MARK AS OVER ANNOTATED | Summary: response to xenobiotic stimulus is treated as over-annotation because it is contextual or downstream of Crot's direct role (IDA, PMID:11023836). Reason: The paper shows that the drug etomoxir irreversibly inhibits rat COT and maps the inhibitor-sensitive histidines (H131, H340). Being the molecular target of a drug is a property of the enzyme, not participation by Crot in a cellular or organismal response to the xenobiotic, so the process term overshoots what was measured. The informative result is captured by the carnitine O-octanoyltransferase activity annotation from the same paper. Supporting Evidence: PMID:11023836 Rat peroxisomal carnitine octanoyltransferase (COT), which facilitates the transport of medium-chain fatty acids through the peroxisomal membrane, is irreversibly inhibited by the hypoglycaemia-inducing drug etomoxir. PMID:11023836 these results indicate that the two histidine residues, H131 and H340, are the sites responsible for inhibition by etomoxir |
| GO:0071874 cellular response to norepinephrine stimulus | HEP PMID:14618266 Gene expression profile of cardiomyocytes in hypertrophic he... | MARK AS OVER ANNOTATED | Summary: cellular response to norepinephrine stimulus is treated as over-annotation because it is contextual or downstream of Crot's direct role (HEP, PMID:14618266). Reason: Crot mRNA co-clustered with energy-metabolism genes in a microarray time course of cardiomyocytes from norepinephrine-infused rats. An expression change during in vivo infusion does not show that Crot performs any step of a cellular response to norepinephrine, so the term overshoots the expression evidence. Supporting Evidence: PMID:14618266 One set consisted of several enzymes involved in energy metabolism, including carnitine octanoyltransferase, ATP synthase subunit c, pancreatic lipase and glycogen phosphorylase |
| GO:0001579 medium-chain fatty acid transport | TAS PMID:11790793 Structural model of a malonyl-CoA-binding site of carnitine ... | ACCEPT | Summary: Crot's peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation supports retaining medium-chain fatty acid transport as a direct annotation (TAS, PMID:11790793). Reason: medium-chain fatty acid transport is a direct process-level consequence of Crot's documented role in peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation. Supporting Evidence: PMID:11790793 Carnitine octanoyltransferase (COT) and carnitine palmitoyltransferase (CPT) I, which facilitate the transport of medium- and long-chain fatty acids through the peroxisomal and mitochondrial membranes, are physiologically inhibited by malonyl-CoA. file:rat/Crot/Crot-deep-research-falcon.md CROT is explicitly presented as a key component of a **carnitine-dependent transport mechanism** exporting ฮฒ-oxidation products to mitochondria for further metabolism. |
| GO:0008458 carnitine O-octanoyltransferase activity | TAS PMID:7495866 Molecular cloning and sequence analysis of the rat liver car... | ACCEPT | Summary: Crot's peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation supports retaining carnitine O-octanoyltransferase activity as a direct annotation (TAS, PMID:7495866). Reason: carnitine O-octanoyltransferase activity directly matches Crot's documented role in peroxisomal medium-chain acyl-CoA transfer to carnitine during fatty acid beta-oxidation. Supporting Evidence: PMID:7495866 The full-length cDNA and the natural gene for rat peroxisomal carnitine octanoyltransferase (COT) have been isolated and sequenced. |
| GO:0015909 long-chain fatty acid transport | TAS PMID:11790793 Structural model of a malonyl-CoA-binding site of carnitine ... | MARK AS OVER ANNOTATED | Summary: Long-chain fatty acid transport, traceable to a sentence in PMID:11790793 that pairs COT with medium-chain and CPT I with long-chain fatty acid transport (TAS). Reason: In the source sentence the long-chain half describes CPT I at the mitochondrial membrane; the COT half is medium-chain transport, which the gene already carries from the same paper (GO:0001579, ACCEPT). GO:0001579 is a sibling of GO:0015909, not a descendant, so the earlier MODIFY to it was neither a refinement nor new coverage. Purified rat COT does act on acyl chains up to C20 with a hexanoyl optimum, so a minor long-chain contribution is not excluded and the row is marked as over-annotated rather than removed. Supporting Evidence: PMID:6630173 COT exhibited activity with all of the substrates tested (acyl-CoA's and acylcarnitines of saturated fatty acids having carbon chain lengths of C2--C20), though maximum activity was observed with hexanoyl derivatives. PMID:11790793 Carnitine octanoyltransferase (COT) and carnitine palmitoyltransferase (CPT) I, which facilitate the transport of medium- and long-chain fatty acids through the peroxisomal and mitochondrial membranes, are physiologically inhibited by malonyl-CoA. |
| GO:0015908 fatty acid transport | ISO GO_REF:0000121 | MODIFY | Summary: fatty acid transport captures part of Crot biology, but a more specific replacement better represents the direct role (ISO, GO_REF:0000121). Reason: fatty acid transport is directionally related to Crot but should be replaced by the more specific term(s): medium-chain fatty acid transport. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:1921364 ยท mouse Crot SUPPORTS SOURCE BUT NOT TARGET The mouse Crot donor evidence concerns medium-chain acyl export from peroxisomes; the generic fatty acid transport parent understates that specificity. Proposed replacements: medium-chain fatty acid transport Supporting Evidence: UniProtKB:P11466 FUNCTION: Beta-oxidation of fatty acids. The highest activity concerns the C6 to C10 chain length substrate. |
| GO:0005777 peroxisome | ISO GO_REF:0000121 | ACCEPT | Summary: ISO from human CROT (UniProtKB:Q9UKG9), a donor-split sibling of the mouse-donor peroxisome ISO row. Peroxisomal localization of COT is conserved and directly shown for the rat enzyme. Reason: Peroxisomal localization is the defining location of Crot (C-terminal AHL peroxisomal targeting signal; enzyme purified from rat liver peroxisomes), and the peroxisome is where it converts medium-chain and branched-chain beta-oxidation products to acylcarnitines for export, so it is accepted as the core location. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q9UKG9 ยท CROT SUPPORTS TRANSFER Human CROT donor; peroxisomal localization is conserved and independently shown for rat COT (PMID:6630173). Supporting Evidence: UniProtKB:P11466 SUBCELLULAR LOCATION: Peroxisome PMID:6630173 COT was found in peroxisomes and the soluble compartment but not in mitochondria |
| GO:0006631 fatty acid metabolic process | ISO GO_REF:0000121 | ACCEPT | Summary: ISO from human CROT (UniProtKB:Q9UKG9), a donor-split sibling of the mouse-donor row for the same term. Human COT converts the pristanic acid beta-oxidation product 4,8-dimethylnonanoyl-CoA to its carnitine ester, and rat COT acts on C2-C20 acyl-CoAs with a medium-chain optimum. Reason: Crot directly converts fatty acyl-CoAs to acylcarnitines, a step in fatty acid metabolism; the general term is accepted alongside the more specific medium-chain fatty acid metabolic process and fatty acid beta-oxidation annotations. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q9UKG9 ยท CROT SUPPORTS TRANSFER Human CROT donor, whose fatty acid metabolism role rests on its enzymology (PMID:10486279); the same activity is documented for rat COT. Supporting Evidence: PMID:10486279 Enzyme activity measurements showed that COT efficiently converts one of the end products of the peroxisomal beta-oxidation of pristanic acid, 4, 8-dimethylnonanoyl-CoA, to its corresponding carnitine ester. PMID:6630173 COT exhibited activity with all of the substrates tested (acyl-CoA's and acylcarnitines of saturated fatty acids having carbon chain lengths of C2--C20), though maximum activity was observed with hexanoyl derivatives. |
| GO:0008458 carnitine O-octanoyltransferase activity | ISO GO_REF:0000121 | ACCEPT | Summary: ISO from human CROT (UniProtKB:Q9UKG9), a donor-split sibling of the mouse-donor activity row. Carnitine O-octanoyltransferase activity is shown directly for recombinant human COT and for purified and recombinant rat COT. Reason: Core activity conserved between orthologs and directly demonstrated for the rat enzyme (PMID:6630173, PMID:11023836). Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q9UKG9 ยท CROT SUPPORTS TRANSFER Human CROT donor with direct enzymatic evidence (PMID:10486279); the activity is shared by the rat ortholog. Supporting Evidence: PMID:10486279 Enzyme activity measurements showed that COT efficiently converts one of the end products of the peroxisomal beta-oxidation of pristanic acid, 4, 8-dimethylnonanoyl-CoA, to its corresponding carnitine ester. UniProtKB:P11466 Reaction=octanoyl-CoA + (R)-carnitine = O-octanoyl-(R)-carnitine + CoA; |
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