cpt2 encodes mitochondrial carnitine O-palmitoyltransferase 2, the inner-membrane-facing enzyme of the carnitine shuttle. It converts long-chain acylcarnitines back to acyl-CoA in the mitochondrial matrix side, enabling long-chain fatty acids to enter beta-oxidation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: mitochondrion (GO:0005739) is reviewed for zebrafish cpt2. This annotation is biologically plausible, but it is not the most informative core function for cpt2. Falcon deep research provides direct zebrafish-specific localization evidence: CPT2 protein was detected by Western blot in mitochondrial fractions isolated from zebrafish larvae, confirming the gene product localizes to mitochondria. The more specific term GO:0005743 (mitochondrial inner membrane) better captures the localization. Reason: Mitochondrion localization is correct but less specific than mitochondrial inner membrane. Supporting Evidence: file:DANRE/cpt2/cpt2-uniprot.txt FUNCTION: Involved in the intramitochondrial synthesis of acyl-CoAs for beta-oxidation from long-chain acylcarnitines. file:DANRE/cpt2/cpt2-deep-research-falcon.md In zebrafish specifically, CPT2 protein was experimentally detected by Western blot in **mitochondrial fractions** isolated from larvae, providing direct evidence that the zebrafish cpt2 gene product localizes to mitochondria (consistent with mitochondrial targeting signals in CPT2 proteins). PMID:39199302 A representative Western blot of CPT2 protein levels isolated from the mitochondrial fraction |
| GO:0004095 carnitine O-palmitoyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: carnitine O-palmitoyltransferase activity (GO:0004095) is reviewed for zebrafish cpt2. The annotation is consistent with the curated UniProt/GOA record and the synthesized function of carnitine O-palmitoyltransferase 2. Falcon deep research confirms the conserved catalytic role (reconversion of long-chain acylcarnitines to acyl-CoA) and reports ~70.9% sequence homology between zebrafish cpt2 and human CPT2, strengthening this phylogenetic inference. Reason: This term directly reflects the supported carnitine O-palmitoyltransferase 2 role: FUNCTION: Involved in the intramitochondrial synthesis of acyl-CoAs for beta-oxidation from long-chain acylcarnitines. Supporting Evidence: file:DANRE/cpt2/cpt2-uniprot.txt FUNCTION: Involved in the intramitochondrial synthesis of acyl-CoAs for beta-oxidation from long-chain acylcarnitines. file:DANRE/cpt2/cpt2-deep-research-falcon.md **CPT2βs core biochemical role** is to **reconvert fatty acylcarnitines to fatty acyl-CoA** at/near the **inner mitochondrial membrane**, releasing free carnitine for recycling. PMID:39199302 carnitine palmitoyltransferase 2 (CPT2) that converts the long-chain acylcarnitine to acyl-CoA for oxidation in the inner mitochondrial membrane. |
| GO:0006635 fatty acid beta-oxidation | IBA GO_REF:0000033 | ACCEPT | Summary: fatty acid beta-oxidation (GO:0006635) is reviewed for zebrafish cpt2. The annotation is consistent with the curated UniProt/GOA record and the synthesized function of carnitine O-palmitoyltransferase 2. Falcon deep research provides direct zebrafish in vivo evidence: morpholino knockdown of zebrafish cpt2 caused significant accumulation of long-chain fatty-acylcarnitines (including C16, C18, C18:1), the hallmark metabolic consequence of a block at the CPT2 step (impaired reconversion of acylcarnitines to acyl-CoA for beta-oxidation). Reason: This term directly reflects the supported carnitine O-palmitoyltransferase 2 role: FUNCTION: Involved in the intramitochondrial synthesis of acyl-CoAs for beta-oxidation from long-chain acylcarnitines. Supporting Evidence: file:DANRE/cpt2/cpt2-uniprot.txt FUNCTION: Involved in the intramitochondrial synthesis of acyl-CoAs for beta-oxidation from long-chain acylcarnitines. file:DANRE/cpt2/cpt2-deep-research-falcon.md LC-MS/MS profiling demonstrated significant increases in long-chain fatty-acylcarnitines in knockdown larvae. file:DANRE/cpt2/cpt2-deep-research-falcon.md consistent with a block at the CPT2 step (i.e., impaired reconversion of acylcarnitines to acyl-CoA for Ξ²-oxidation) |
| GO:0004095 carnitine O-palmitoyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: carnitine O-palmitoyltransferase activity (GO:0004095) is reviewed for zebrafish cpt2. The annotation is consistent with the curated UniProt/GOA record and the synthesized function of carnitine O-palmitoyltransferase 2. Falcon deep research independently supports the carnitine O-palmitoyltransferase activity, noting CPT2 acts on medium/long-chain acyl-CoA esters (C8-C18), with a crystal structure complexed with CoA and palmitate (C16). Reason: This term directly reflects the supported carnitine O-palmitoyltransferase 2 role: FUNCTION: Involved in the intramitochondrial synthesis of acyl-CoAs for beta-oxidation from long-chain acylcarnitines. Supporting Evidence: file:DANRE/cpt2/cpt2-uniprot.txt FUNCTION: Involved in the intramitochondrial synthesis of acyl-CoAs for beta-oxidation from long-chain acylcarnitines. file:DANRE/cpt2/cpt2-deep-research-falcon.md CPT1/CPT2 are specific for **long-chain fatty acyl-CoAs, reported as C8βC18**, and discusses a CPT2 crystal structure complexed with CoA and palmitate (C16), reinforcing preference for medium-to-long saturated acyl groups typical of LCFA oxidation. |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | ACCEPT | Summary: mitochondrial inner membrane (GO:0005743) is reviewed for zebrafish cpt2. The annotation is consistent with the curated UniProt/GOA record and the synthesized function of carnitine O-palmitoyltransferase 2. Falcon deep research reinforces this: CPT2 is consistently placed at the inner mitochondrial membrane where it reconverts acylcarnitines to acyl-CoA on the matrix side, and zebrafish CPT2 was detected in mitochondrial fractions. This is the most informative localization term for cpt2 and represents the core function localization. Reason: This term directly reflects the supported carnitine O-palmitoyltransferase 2 role: FUNCTION: Involved in the intramitochondrial synthesis of acyl-CoAs for beta-oxidation from long-chain acylcarnitines. Supporting Evidence: file:DANRE/cpt2/cpt2-uniprot.txt FUNCTION: Involved in the intramitochondrial synthesis of acyl-CoAs for beta-oxidation from long-chain acylcarnitines. file:DANRE/cpt2/cpt2-deep-research-falcon.md CPT2 is consistently placed at the **inner mitochondrial membrane** and described as more **matrix-facing / matrix-protein-like** than CPT1. PMID:39199302 carnitine palmitoyltransferase 2 (CPT2) that converts the long-chain acylcarnitine to acyl-CoA for oxidation in the inner mitochondrial membrane. |
| GO:0008458 carnitine O-octanoyltransferase activity | IEA GO_REF:0000116 | KEEP AS NON CORE | Summary: carnitine O-octanoyltransferase activity (GO:0008458) is reviewed for zebrafish cpt2. This annotation is biologically plausible, but it is not the most informative core function for cpt2. Falcon deep research is consistent: CPT2 is active on mid-length (medium-chain, e.g. C8) as well as long-chain acyl-CoA esters, with virtually no activity on short-chain or ultralong-chain substrates. Octanoyl (C8) transferase activity is therefore a chain-length variant of the canonical long-chain palmitoyltransferase activity, supporting retention as non-core. Reason: Carnitine O-octanoyltransferase activity is supported as an acyl-chain variant activity, but palmitoyltransferase activity captures the canonical CPT2 role. Supporting Evidence: file:DANRE/cpt2/cpt2-uniprot.txt FUNCTION: Involved in the intramitochondrial synthesis of acyl-CoAs for beta-oxidation from long-chain acylcarnitines. file:DANRE/cpt2/cpt2-deep-research-falcon.md CPT2 is catalytically active on **mid-length and long-chain acyl-CoA esters**, but βvirtually no activityβ is observed on **short-chain** and **ultralong-chain** acyl-CoAs |
| GO:0015909 long-chain fatty acid transport | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: long-chain fatty acid transport (GO:0015909) is reviewed for zebrafish cpt2. The annotation reflects cpt2's participation in the carnitine shuttle, the pathway that delivers long-chain fatty acyl groups across the mitochondrial membranes for beta-oxidation. Falcon deep research clarifies the mechanism: CPT2 itself acts enzymatically (reconverting acylcarnitine to acyl-CoA on the matrix side of the inner membrane), while the actual membrane translocation step is performed by the carnitine/acylcarnitine translocase (CACT). cpt2 is thus a downstream component enabling the net transport process rather than a transporter itself; keeping this process-level annotation is reasonable but it should be understood as the carnitine-shuttle (transport) pathway context rather than direct transporter activity. Reason: cpt2 contributes to the net long-chain fatty acid transport process via its enzymatic role in the carnitine shuttle, but it is not itself a fatty acid transporter (membrane translocation is performed by CACT). The annotation is retained as a non-core pathway-context term; the core function is the carnitine O-palmitoyltransferase activity and downstream beta-oxidation. Supporting Evidence: file:DANRE/cpt2/cpt2-uniprot.txt FUNCTION: Involved in the intramitochondrial synthesis of acyl-CoAs for beta-oxidation from long-chain acylcarnitines. file:DANRE/cpt2/cpt2-deep-research-falcon.md CPT1 converts fatty acyl-CoA to acylcarnitine, CACT transports it, and **CPT2 βuncouplesβ it back to fatty acyl-CoA + L-carnitine at the inner mitochondrial membrane**, enabling entry into Ξ²-oxidation. |
| GO:0016746 acyltransferase activity | IEA GO_REF:0000002 | MODIFY | Summary: acyltransferase activity (GO:0016746) is reviewed for zebrafish cpt2. The annotation captures the right biochemical family but is less specific than the characterized carnitine O-palmitoyltransferase 2 activity. Falcon deep research confirms cpt2 is a carnitine acyltransferase specialized for long-chain fatty acyl groups (C8-C18), so the broad acyltransferase term should be modified to the specific carnitine O-palmitoyltransferase activity. Reason: The broad term is true but under-informative. The specific supported term for cpt2 is carnitine O-palmitoyltransferase activity. Proposed replacements: carnitine O-palmitoyltransferase activity Supporting Evidence: file:DANRE/cpt2/cpt2-uniprot.txt FUNCTION: Involved in the intramitochondrial synthesis of acyl-CoAs for beta-oxidation from long-chain acylcarnitines. file:DANRE/cpt2/cpt2-deep-research-falcon.md CPT1/CPT2 are specific for **long-chain fatty acyl-CoAs, reported as C8βC18** |
| GO:0006635 fatty acid beta-oxidation | IEA GO_REF:0000041 | ACCEPT | Summary: fatty acid beta-oxidation (GO:0006635) is reviewed for zebrafish cpt2. The annotation is consistent with the curated UniProt/GOA record and the synthesized function of carnitine O-palmitoyltransferase 2. Falcon deep research supports this process role: cpt2 enables long-chain fatty acids to enter matrix beta-oxidation, and its loss in zebrafish produces the expected acylcarnitine accumulation. This is a core process for cpt2. Reason: This term directly reflects the supported carnitine O-palmitoyltransferase 2 role: FUNCTION: Involved in the intramitochondrial synthesis of acyl-CoAs for beta-oxidation from long-chain acylcarnitines. Supporting Evidence: file:DANRE/cpt2/cpt2-uniprot.txt FUNCTION: Involved in the intramitochondrial synthesis of acyl-CoAs for beta-oxidation from long-chain acylcarnitines. file:DANRE/cpt2/cpt2-deep-research-falcon.md Long-chain fatty acids (LCFAs) are oxidized in the **mitochondrial matrix** via Ξ²-oxidation |
| GO:0004095 carnitine O-palmitoyltransferase activity | ISS GO_REF:0000024 | ACCEPT | Summary: carnitine O-palmitoyltransferase activity (GO:0004095) is reviewed for zebrafish cpt2. The annotation is consistent with the curated UniProt/GOA record and the synthesized function of carnitine O-palmitoyltransferase 2. This ISS annotation transfers from human CPT2 (P23786); falcon deep research confirms the ~70.9% sequence homology between zebrafish cpt2 and human CPT2 that underpins this inference. Reason: This term directly reflects the supported carnitine O-palmitoyltransferase 2 role: FUNCTION: Involved in the intramitochondrial synthesis of acyl-CoAs for beta-oxidation from long-chain acylcarnitines. Supporting Evidence: file:DANRE/cpt2/cpt2-uniprot.txt FUNCTION: Involved in the intramitochondrial synthesis of acyl-CoAs for beta-oxidation from long-chain acylcarnitines. file:DANRE/cpt2/cpt2-deep-research-falcon.md reports **~70.9% sequence homology** between zebrafish cpt2 and human CPT2, supporting that βcpt2β in zebrafish refers to the same conserved enzyme class as the UniProt record. PMID:39199302 Human Cpt2 (ENSG00000157184) and zebrafish cpt2 (ENSDARG00000038618) are homologous (www.zfin.org) and the sequences show 70.9% alignment as determined by Expasy (www.expasy.org). |
| GO:0008458 carnitine O-octanoyltransferase activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: carnitine O-octanoyltransferase activity (GO:0008458) is reviewed for zebrafish cpt2. This annotation is biologically plausible, but it is not the most informative core function for cpt2. Falcon deep research indicates CPT2 is active on mid-length (e.g. octanoyl, C8) as well as long-chain acyl-CoA esters; octanoyltransferase activity is therefore a chain-length variant of the canonical long-chain palmitoyltransferase activity. Reason: Carnitine O-octanoyltransferase activity is supported as an acyl-chain variant activity, but palmitoyltransferase activity captures the canonical CPT2 role. Supporting Evidence: file:DANRE/cpt2/cpt2-uniprot.txt FUNCTION: Involved in the intramitochondrial synthesis of acyl-CoAs for beta-oxidation from long-chain acylcarnitines. file:DANRE/cpt2/cpt2-deep-research-falcon.md A 2024 review summarizes that CPT2 is catalytically active on **mid-length and long-chain acyl-CoA esters**, but βvirtually no activityβ is observed on **short-chain** and **ultralong-chain** acyl-CoAs |
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Download this section (compressed HTML)Reviewed GOA, UniProt Q5U3U3, and PANTHER family cache. The core role is mitochondrial inner-membrane carnitine O-palmitoyltransferase activity in long-chain fatty-acid beta-oxidation; generic acyltransferase and octanoyltransferase terms were treated as less specific/non-core relative to CPT2 activity.
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