cpt2

UniProt ID: Q5U3U3
Organism: Danio rerio
Review Status: DRAFT
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Gene Description

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.

Existing Annotations Review

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
**CPT2’s 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 β-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 C8–C18**, 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 “virtually no activity” 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 “uncouples” it back to fatty acyl-CoA + L-carnitine at the inner mitochondrial membrane**, enabling entry into β-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.
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 C8–C18**
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 β-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 “cpt2” 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 “virtually no activity” is observed on **short-chain** and **ultralong-chain** acyl-CoAs

Core Functions

cpt2 performs carnitine O-palmitoyltransferase activity as carnitine O-palmitoyltransferase 2, with activity localized primarily to mitochondrial inner membrane and directly supporting mitochondrial fatty acid beta-oxidation by regenerating acyl-CoAs from long-chain acylcarnitines.

Molecular Function:
carnitine O-palmitoyltransferase activity
Directly Involved In:
fatty acid beta-oxidation
Cellular Locations:
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
    **CPT2’s 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.

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000024
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000041
Gene Ontology annotation based on UniPathway vocabulary mapping
GO_REF:0000044
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
GO_REF:0000116
Automatic Gene Ontology annotation based on Rhea mapping
GO_REF:0000117
Electronic Gene Ontology annotations created by ARBA machine learning models
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
file:DANRE/cpt2/cpt2-uniprot.txt
UniProtKB entry Q5U3U3 for Danio rerio cpt2
  • FUNCTION: Involved in the intramitochondrial synthesis of acyl-CoAs for beta-oxidation from long-chain acylcarnitines.
    "FUNCTION: Involved in the intramitochondrial synthesis of acyl-CoAs for beta-oxidation from long-chain acylcarnitines."
file:DANRE/cpt2/cpt2-deep-research-falcon.md
Falcon deep research report on Danio rerio cpt2 (Q5U3U3)
  • Zebrafish cpt2 is the Danio rerio ortholog of human CPT2 (~70.9% sequence homology) and encodes a mitochondrial carnitine O-palmitoyltransferase 2 that reconverts long-chain acylcarnitines to acyl-CoA at the inner mitochondrial membrane as part of the carnitine shuttle, enabling long-chain fatty acid beta-oxidation.
    "Independent zebrafish experimental work explicitly targets zebrafish **cpt2** as the ortholog of human CPT2 and reports **~70.9% sequence homology** between zebrafish cpt2 and human CPT2, supporting that “cpt2” in zebrafish refers to the same conserved enzyme class as the UniProt record."
  • The core biochemical role of CPT2 is to reconvert fatty acylcarnitines to fatty acyl-CoA at/near the inner mitochondrial membrane, releasing free carnitine for recycling; CPT1 makes acylcarnitine, CACT transports it, and CPT2 uncouples it back to acyl-CoA + L-carnitine for matrix beta-oxidation.
    "**CPT2’s core biochemical role** is to **reconvert fatty acylcarnitines to fatty acyl-CoA** at/near the **inner mitochondrial membrane**, releasing free carnitine for recycling. A recent review describes the sequential steps: CPT1 converts fatty acyl-CoA to acylcarnitine, CACT transports it, and **CPT2 “uncouples” it back to fatty acyl-CoA + L-carnitine at the inner mitochondrial membrane**, enabling entry into β-oxidation."
  • CPT2 is catalytically active on mid-length and long-chain acyl-CoA esters (C8-C18) with virtually no activity on short-chain or ultralong-chain substrates, consistent with its canonical role in long-chain fatty acid oxidation.
    "A 2024 review summarizes that CPT2 is catalytically active on **mid-length and long-chain acyl-CoA esters**, but “virtually no activity” is observed on **short-chain** and **ultralong-chain** acyl-CoAs (and some non-fatty-acyl substrates), which is consistent with CPT2’s canonical role in LCFA oxidation rather than short-chain metabolism."
  • In zebrafish, CPT2 protein was detected by Western blot in mitochondrial fractions from larvae, providing direct evidence that the cpt2 gene product localizes to mitochondria.
    "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)."
  • Morpholino knockdown of zebrafish cpt2 caused significant accumulation of long-chain fatty-acylcarnitines, the expected metabolic consequence of a block at the CPT2 step (impaired reconversion of acylcarnitines to acyl-CoA for beta-oxidation).
    "LC-MS/MS profiling demonstrated significant increases in long-chain fatty-acylcarnitines in knockdown larvae. Total acylcarnitines increased by approximately **~70% (translation-blocking; p<0.001)** and **~42% (splice-blocking; p≤0.05)** versus wild-type, consistent with a block at the CPT2 step (i.e., impaired reconversion of acylcarnitines to acyl-CoA for β-oxidation)."
PMID:39199302
Cpt2 Deficiency Modeled in Zebrafish: Abnormal Neural Development, Electrical Activity, Behavior, and Schizophrenia-Related Gene Expression
  • Zebrafish cpt2 and human CPT2 are orthologous, sharing 70.9% sequence alignment, supporting use of zebrafish as a model for CPT2 function.
    "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)."
  • CPT2 is an inner mitochondrial membrane enzyme of the carnitine shuttle that converts long-chain acylcarnitine to acyl-CoA for beta-oxidation.
    "carnitine palmitoyltransferase 2 (CPT2) that converts the long-chain acylcarnitine to acyl-CoA for oxidation in the inner mitochondrial membrane."
  • Zebrafish CPT2 protein was detected in isolated mitochondrial fractions from larvae by Western blot, confirming mitochondrial localization.
    "A representative Western blot of CPT2 protein levels isolated from the mitochondrial fraction"

Deep Research

Falcon

(cpt2-deep-research-falcon.md)
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 23 citations 2 artifacts 2026-05-30T03:29:32.228001
Edison artifact artifact-00 (text/markdown)
## Context ID: pqac-00000008 The requested data on acylcarnitine levels and CPT2 localization can be found in Figure 2 on page 10. - **Acylcarnitine levels:** F (image/png)

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research report: Functional annotation of Danio rerio cpt2 (UniProt Q5U3U3) encoding mitochondrial carnitine O-palmitoyltransferase 2 (CPT2; EC 2.3.1.21)

1) Identity verification (mandatory)

The UniProt entry provided (Q5U3U3) describes Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2) in zebrafish (Danio rerio) and places it in the carnitine/choline acyltransferase family, consistent with the CPT2 literature describing a mitochondrial carnitine acyltransferase that is part of the carnitine shuttle for long-chain fatty-acid oxidation. Independent zebrafish experimental work explicitly targets zebrafish cpt2 as the ortholog of human CPT2 and reports ~70.9% sequence homology between zebrafish cpt2 and human CPT2, supporting that “cpt2” in zebrafish refers to the same conserved enzyme class as the UniProt record. (baker2024cpt2deficiencymodeled pages 2-4)

2) Key concepts and current understanding

2.1 The carnitine shuttle (CPT system) and why CPT2 is required

Long-chain fatty acids (LCFAs) are oxidized in the mitochondrial matrix via β-oxidation, but long-chain acyl-CoA species do not freely cross the inner mitochondrial membrane. The canonical “carnitine shuttle” solves this by interconverting acyl-CoA and acylcarnitines and transporting the acyl moiety across mitochondrial membranes.

CPT2’s core biochemical role is to reconvert fatty acylcarnitines to fatty acyl-CoA at/near the inner mitochondrial membrane, releasing free carnitine for recycling. A recent review describes the sequential steps: CPT1 converts fatty acyl-CoA to acylcarnitine, CACT transports it, and CPT2 “uncouples” it back to fatty acyl-CoA + L-carnitine at the inner mitochondrial membrane, enabling entry into β-oxidation. (duan2024theroleof pages 2-4)

A mechanistic description from an authoritative medicinal chemistry review similarly states that once acylcarnitines are inside mitochondrial membranes, they are “reconverted to acyl-CoA by CPT2” to enter the fatty-acid oxidation cycle, and notes CPT2’s location on/associated with the inner mitochondrial membrane and operation on the intramitochondrial side. (ceccarelli2011carnitinepalmitoyltransferase(cpt) pages 1-3)

Reaction (conceptual):
- fatty acylcarnitine + CoA ⇄ fatty acyl-CoA + carnitine (CPT2-catalyzed acyl transfer). (ceccarelli2011carnitinepalmitoyltransferase(cpt) pages 1-3, duan2024theroleof pages 2-4)

2.2 Substrate specificity (chain-length preference)

Across carnitine acyltransferase family discussions, CPT2 is characterized as a medium/long-chain acyltransferase. A 2024 review summarizes that CPT2 is catalytically active on mid-length and long-chain acyl-CoA esters, but “virtually no activity” is observed on short-chain and ultralong-chain acyl-CoAs (and some non-fatty-acyl substrates), which is consistent with CPT2’s canonical role in LCFA oxidation rather than short-chain metabolism. (duan2024theroleof pages 4-5)

A recent structural review of carnitine acyltransferases (including CPT2) explicitly states that CPT1/CPT2 are specific for long-chain fatty acyl-CoAs, reported as C8–C18, 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. (volpicella2025carnitineoacetyltransferaseas pages 8-9)

2.3 Subcellular localization and topology

CPT2 is consistently placed at the inner mitochondrial membrane and described as more matrix-facing / matrix-protein-like than CPT1. A 2024 review contrasts CPT1 (outer membrane-anchored) with CPT2 being “more lightly attached to the internal membrane” and behaving like a matrix protein, consistent with catalysis on the matrix side after CACT transport. (duan2024theroleof pages 4-5)

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). (baker2024cpt2deficiencymodeled pages 4-5, baker2024cpt2deficiencymodeled pages 8-10)

3) Zebrafish-specific functional evidence (Danio rerio)

3.1 2024 zebrafish CPT2 deficiency model (direct experimental evidence)

The most direct Danio rerio functional evidence in the retrieved literature is a 2024 study that knocked down zebrafish cpt2 using both splice-blocking and translation-blocking morpholinos and then assessed protein levels and metabolite consequences.

Knockdown efficacy (mitochondrial protein): Western blots from zebrafish mitochondrial fractions showed that translation-blocking knockdown reduced CPT2 protein by ~31% vs control (not statistically significant in the excerpt), while splice-blocking knockdown reduced CPT2 by ~78% vs control (significant). (baker2024cpt2deficiencymodeled pages 8-10)

Metabolic readout (acylcarnitines): LC-MS/MS profiling demonstrated significant increases in long-chain fatty-acylcarnitines in knockdown larvae. Total acylcarnitines increased by approximately ~70% (translation-blocking; p<0.001) and ~42% (splice-blocking; p≤0.05) versus wild-type, consistent with a block at the CPT2 step (i.e., impaired reconversion of acylcarnitines to acyl-CoA for β-oxidation). (baker2024cpt2deficiencymodeled pages 8-10)

Developmental/organismal phenotypes: CPT2 knockdown zebrafish showed abnormal lipid utilization and deposition, reduced body size, abnormal brain development, altered axonal projections and neurotransmitter synthesis, electrical hyperactivity, and disrupted swimming behavior; the authors also report increased expression of schizophrenia-associated genes, linking CPT2-dependent fatty-acid oxidation and acylcarnitine handling to neurodevelopmental outcomes in a vertebrate model. (baker2024cpt2deficiencymodeled pages 1-2, baker2024cpt2deficiencymodeled pages 25-26)

Zebrafish model usability: The authors chose a 0.5 mM morpholino dose because early viability at 1 day post-injection was comparable across groups (WT 77%; control 84%; TB 74%; SB 79%), supporting a “mild-to-moderate” deficiency model rather than a lethal severe model. (baker2024cpt2deficiencymodeled pages 8-10)

Figure-based evidence: The study’s Figure 2 includes (i) CPT2 Western blot data in mitochondrial fractions and (ii) total acylcarnitine increases by LC-MS/MS. (baker2024cpt2deficiencymodeled media c22cb2e6)

3.2 Zebrafish systems-level context: environmental disruption of the carnitine shuttle (2024)

A 2024 systems toxicology study integrated published zebrafish omics datasets using a stoichiometric zebrafish metabolic model and concluded that PFOS exposure prominently impacts the carnitine shuttle and fatty-acid oxidation. The model used PFOS parameterization at 0.06, 0.6, and 2 µM and predicted fatty acid and acyl-CoA pool changes with flux increases by “almost an order of magnitude,” consistent with dyslipidemia-like shifts. While this work does not isolate cpt2 alone, it supports real-world relevance of the pathway in zebrafish environmental exposures. (nolen2024insilicobiomarker pages 8-9)

3.3 Nutritional modulation of the carnitine pool in zebrafish (background implementation)

A zebrafish dietary study shows that increasing carnitine availability can increase mitochondrial β-oxidation capacity and reduce tissue lipid deposition; mechanistically this would tend to increase flux through the CPT/CACT/CPT2 shuttle (even though the excerpt highlights CPT1 transcriptional induction more than CPT2). Dietary L-carnitine significantly increased free/total carnitine in tissues, significantly decreased triglycerides in liver and muscle, and significantly increased mitochondrial and total β-oxidation capacity in liver (feeding and fasting) and muscle (feeding). (li2017systemicregulationof pages 2-4)

4) Recent developments and current research directions (prioritizing 2023–2024)

4.1 Expanding disease/pathway connections (2023–2024 reviews)

Although much CPT2 literature is human-disease oriented, recent reviews emphasize CPT2 dysfunction in metabolic disease contexts and highlight mechanism-level thinking that is transferable to zebrafish functional annotation because the enzyme role is conserved.

  • CPT2 in NAFLD/MAFLD progression: A 2023 review frames CPT-II as an inner mitochondrial membrane protein central to LCFA entry into mitochondrial FAO and discusses how CPT-II dysfunction is observed in models of liver lipid accumulation; it describes CPT-II’s role in converting acylcarnitines to acyl-CoA and recycling carnitine via CACT. (yao2023mitochondrialcarnitinepalmitoyltransferaseii pages 2-4)
  • CPT family functional synthesis (2024): A 2024 review summarizes CPT family membrane topology and explicitly describes CPT2 as the inner membrane enzyme that “uncouples” acylcarnitines to acyl-CoA for matrix β-oxidation, and it also summarizes chain-length activity preferences (mid/long-chain active; short/ultralong inactive). (duan2024theroleof pages 4-5, duan2024theroleof pages 2-4)

4.2 Structural/mechanistic detail relevant to functional inference

Mechanistic understanding of CPT2 is supported by structural analyses. The 2011 medicinal chemistry review describes CPT2 as a shorter protein than CPT1 and summarizes structural binding architecture (distinct CoA, acyl, and carnitine binding sites) and key residues implicated in catalysis and substrate binding; these mechanistic insights support functional inference for zebrafish CPT2 given orthology and shared family domains. (ceccarelli2011carnitinepalmitoyltransferase(cpt) pages 3-4)

5) Current applications and real-world implementations

  1. Zebrafish model for CPT2 deficiency and neurodevelopmental consequences: The 2024 zebrafish knockdown study demonstrates a tractable vertebrate model connecting mitochondrial LCFA oxidation defects (acylcarnitine accumulation) to brain development, electrophysiology, and behavior, supporting use in functional genomics and metabolic-neurodevelopment research. (baker2024cpt2deficiencymodeled pages 1-2, baker2024cpt2deficiencymodeled pages 8-10)

  2. Environmental monitoring/toxicology using carnitine-shuttle biomarkers: The 2024 PFOS systems biology work suggests the carnitine shuttle (in which CPT2 is an essential component) can be a focal pathway for pollutant-associated metabolic dysregulation in aquatic organisms; the authors highlight carnitine as a candidate biomarker in field studies, illustrating translational eco-toxicology implementation. (nolen2024insilicobiomarker pages 8-9)

  3. Nutrition/aquaculture physiology: Dietary carnitine supplementation experiments in zebrafish show a practical intervention that modulates lipid deposition and mitochondrial β-oxidation capacity, underscoring the applied importance of carnitine-shuttle capacity for fish metabolism and potentially informing aquaculture strategies. (li2017systemicregulationof pages 2-4)

  4. Drug discovery and CPT pathway modulation (broader context): Reviews of CPT enzymes (including CPT2) discuss pharmacologic modulation of the CPT system as a long-standing strategy in metabolic disease and cancer metabolism research. While these are not zebrafish-specific applications, they contextualize CPT2 as part of a druggable metabolic axis. (ceccarelli2011carnitinepalmitoyltransferase(cpt) pages 1-3, duan2024theroleof pages 4-5)

6) Expert synthesis and interpretation (evidence-weighted)

High-confidence functional annotation for zebrafish CPT2 can be made because (i) CPT2’s enzymatic role in the carnitine shuttle is supported by multiple authoritative reviews, and (ii) zebrafish experiments directly show that reducing CPT2 protein in mitochondrial fractions causes acylcarnitine accumulation—a hallmark consequence expected when the acylcarnitine→acyl-CoA reconversion step is impaired. (duan2024theroleof pages 2-4, ceccarelli2011carnitinepalmitoyltransferase(cpt) pages 1-3, baker2024cpt2deficiencymodeled pages 8-10)

Species-specific nuance: The strongest zebrafish-specific evidence currently retrieved is morpholino-based knockdown rather than stable knockout or purified-enzyme kinetics; thus, zebrafish CPT2 substrate specificity is best stated as inferred from conserved CPT2 biochemistry (medium/long-chain preference) rather than as directly measured kinetic constants in Danio rerio, although acylcarnitine accumulation in vivo is consistent with impaired long-chain acyl flux. (duan2024theroleof pages 4-5, volpicella2025carnitineoacetyltransferaseas pages 8-9, baker2024cpt2deficiencymodeled pages 8-10)

7) Key quantitative findings (selected statistics)

  • Zebrafish CPT2 knockdown efficiency: ~31% reduction (TB, vs CTRL) and ~78% reduction (SB, vs CTRL) in mitochondrial CPT2 protein. (baker2024cpt2deficiencymodeled pages 8-10)
  • Acylcarnitine accumulation in zebrafish: total acylcarnitines increased ~70% (TB; p<0.001) and ~42% (SB; p≤0.05) vs WT. (baker2024cpt2deficiencymodeled pages 8-10)
  • PFOS modeling in zebrafish systems toxicology: PFOS simulated at 0.06–2 µM; predicted fatty acid/acyl-CoA pool flux increases by almost an order of magnitude. (nolen2024insilicobiomarker pages 8-9)

Evidence summary table

Claim Evidence type Key quantitative/statistical details Source (citation id + DOI URL + pub month/year)
Identity/function: zebrafish cpt2 is the Danio rerio ortholog of human CPT2 and participates in mitochondrial long-chain fatty-acid β-oxidation by converting long-chain acylcarnitines to acyl-CoA. Zebrafish experiment + comparative annotation Zebrafish/human sequence homology reported as ~70.9%; morpholino knockdown caused abnormal lipid utilization/deposition and neurodevelopmental defects, supporting conserved CPT2 function. Baker et al. 2024, Biomolecules, Jul 2024, https://doi.org/10.3390/biom14080914 (baker2024cpt2deficiencymodeled pages 1-2, baker2024cpt2deficiencymodeled pages 2-4)
Localization: CPT2 is a mitochondrial protein detected in zebrafish mitochondrial fractions, consistent with inner-mitochondrial-membrane carnitine-shuttle localization. Zebrafish experiment CPT2 protein measured in mitochondrial fractions from larvae; Western blot showed zebrafish CPT2 migrating near ~80 kDa. Baker et al. 2024, Biomolecules, Jul 2024, https://doi.org/10.3390/biom14080914 (baker2024cpt2deficiencymodeled pages 8-10, baker2024cpt2deficiencymodeled pages 4-5, baker2024cpt2deficiencymodeled media c22cb2e6)
Loss of function in zebrafish: cpt2 knockdown impairs carnitine-shuttle flux and causes long-chain acylcarnitine accumulation. Zebrafish experiment Translation-blocking MO reduced CPT2 protein by ~31% vs CTRL (~38% vs WT); splice-blocking MO reduced CPT2 by ~78% vs CTRL (~85% vs WT). Total acylcarnitines increased ~70% (TB, p<0.001) and ~42% (SB, p≤0.05) vs WT; long-chain species including C16, C18, C18:1 increased. Baker et al. 2024, Biomolecules, Jul 2024, https://doi.org/10.3390/biom14080914 (baker2024cpt2deficiencymodeled pages 8-10, baker2024cpt2deficiencymodeled pages 25-26)
Phenotype in zebrafish: cpt2 deficiency disrupts development, especially neural and lipid-handling phenotypes. Zebrafish experiment Viability at 1 dpi with 0.5 mM MOs was similar to WT (WT 77%, CTRL 84%, TB 74%, SB 79%), enabling mild–moderate deficiency modeling. Knockdown caused reduced body size, curved tails, pericardial edema, enlarged ventricles, abnormal brain development, altered swimming/electrical activity, and increased schizophrenia-associated gene expression. Baker et al. 2024, Biomolecules, Jul 2024, https://doi.org/10.3390/biom14080914 (baker2024cpt2deficiencymodeled pages 1-2, baker2024cpt2deficiencymodeled pages 25-26, baker2024cpt2deficiencymodeled pages 8-10)
Canonical reaction/pathway: CPT2 reconverts fatty acylcarnitine to fatty acyl-CoA + L-carnitine at the inner mitochondrial membrane as part of the carnitine shuttle. Recent review Places CPT2 at the inner mitochondrial membrane; defines role after CACT-mediated transport so acyl-CoA can enter matrix β-oxidation. Duan et al. 2024, Biology, Nov 2024, https://doi.org/10.3390/biology13110892 (duan2024theroleof pages 2-4)
Substrate specificity/topology: CPT2 behaves as a matrix-facing, inner-membrane-associated carnitine acyltransferase with preference for medium/long-chain substrates. Recent review Reported as catalytically active toward mid-length and long-chain acyl-CoA esters, with little/no activity toward short-chain or ultralong-chain substrates; described as more lightly attached to the inner membrane and matrix-protein-like. Duan et al. 2024, Biology, Nov 2024, https://doi.org/10.3390/biology13110892 (duan2024theroleof pages 4-5)
Carnitine-shuttle context: CPT2 works with CPT1 and CACT to regenerate acyl-CoA on the matrix side of the inner membrane for β-oxidation. Review Describes CPT-II as an IMM protein converting transesterified acylcarnitines into acyl-CoA and releasing carnitine for CACT-mediated return; emphasizes LCFA transport into mitochondria. Yao et al. 2023, World J Gastroenterol, Mar 2023, https://doi.org/10.3748/wjg.v29.i12.1765 (yao2023mitochondrialcarnitinepalmitoyltransferaseii pages 2-4)
Mechanistic/structural support: CPT2 contains distinct CoA-, acyl-, and carnitine-binding sites and lacks the membrane-anchoring N-terminus typical of CPT1. Foundational high-authority review Crystal-structure summary identifies a Y-shaped tunnel with separate CoA/acyl/carnitine sites; key catalytic/binding residues include His372, Tyr486, Ser488, Thr499, Ser590; CPT2 is shorter than CPT1 (658 vs 773 aa) and operates on the matrix side of the inner membrane. Ceccarelli et al. 2011, J Med Chem, Apr 2011, https://doi.org/10.1021/jm100809g (ceccarelli2011carnitinepalmitoyltransferase(cpt) pages 1-3, ceccarelli2011carnitinepalmitoyltransferase(cpt) pages 3-4)
Broader acyltransferase family inference: CPT2 is a carnitine acyltransferase specialized for long-chain fatty acyl groups. Recent review Review states CPT1/CPT2 are specific for long-chain fatty acyl-CoAs (C8–C18) and highlights crystallized CPT2 with CoA and palmitate. Volpicella et al. 2025, Biomolecules, Feb 2025, https://doi.org/10.3390/biom15020216 (volpicella2025carnitineoacetyltransferaseas pages 8-9, volpicella2025carnitineoacetyltransferaseas pages 9-11)
System-level zebrafish application: environmental PFOS exposure perturbs the carnitine shuttle and fatty-acid oxidation in embryo-larval zebrafish, supporting the pathway context in which cpt2 functions. Zebrafish systems biology / real-world implementation In silico zebrafish metabolic model contained 12,909 reactions; PFOS parameterization at 0.06, 0.6, and 2 µM predicted fatty-acid/fatty-acyl-CoA pool flux increases by almost an order of magnitude; human-linked PFOS effects noted at ≤200 ng/mL (≤0.4 µM). Nolen et al. 2024, Front. Syst. Biol., Mar 2024, https://doi.org/10.3389/fsysb.2024.1367562 (nolen2024insilicobiomarker pages 8-9)
Nutritional/metabolic implementation in zebrafish: boosting the carnitine pool enhances mitochondrial β-oxidation and reduces tissue lipid deposition, consistent with higher flux through the CPT shuttle in which CPT2 acts downstream of CPT1. Zebrafish dietary experiment Dietary L-carnitine significantly increased tissue free/total carnitine, significantly decreased liver and muscle TG, and significantly increased mitochondrial and total β-oxidation capacity in liver (feeding and fasting) and muscle (feeding); assays reported n=4 or n=6, significance P<0.05/P<0.01. CPT1 mRNA increased, while lipogenesis genes decreased. Li et al. 2017, Sci Rep, Jan 2017, https://doi.org/10.1038/srep40815 (li2017systemicregulationof pages 2-4, li2017systemicregulationof pages 1-2, li2017systemicregulationof pages 6-7)

Table: This table summarizes the core functional annotation evidence for Danio rerio cpt2 / UniProt Q5U3U3, integrating direct zebrafish experiments with authoritative reviews on CPT2 biochemistry and localization. It is useful for separating species-specific evidence from conserved mechanistic inference.

References (URLs include publication pages)

  • Baker CE et al. CPT2 Deficiency Modeled in Zebrafish. Biomolecules. Jul 2024. https://doi.org/10.3390/biom14080914 (baker2024cpt2deficiencymodeled pages 1-2, baker2024cpt2deficiencymodeled pages 8-10)
  • Duan Y et al. The Role of the CPT Family in Cancer. Biology. Nov 2024. https://doi.org/10.3390/biology13110892 (duan2024theroleof pages 4-5, duan2024theroleof pages 2-4)
  • Nolen RM et al. PFOS exposure and zebrafish metabolism (in silico). Frontiers in Systems Biology. Mar 2024. https://doi.org/10.3389/fsysb.2024.1367562 (nolen2024insilicobiomarker pages 8-9)
  • Yao M et al. CPT-II dysfunction and NAFLD (review). World Journal of Gastroenterology. Mar 2023. https://doi.org/10.3748/wjg.v29.i12.1765 (yao2023mitochondrialcarnitinepalmitoyltransferaseii pages 2-4)
  • Ceccarelli SM et al. CPT modulators (review). Journal of Medicinal Chemistry. Apr 2011. https://doi.org/10.1021/jm100809g (ceccarelli2011carnitinepalmitoyltransferase(cpt) pages 1-3, ceccarelli2011carnitinepalmitoyltransferase(cpt) pages 3-4)
  • Li J-M et al. Dietary L-carnitine in zebrafish. Scientific Reports. Jan 2017. https://doi.org/10.1038/srep40815 (li2017systemicregulationof pages 2-4)

References

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  2. (duan2024theroleof pages 2-4): Yanxia Duan, Jiaxin Liu, Ailin Li, Chang Liu, Guang Shu, and Gang Yin. The role of the cpt family in cancer: searching for new therapeutic strategies. Biology, 13:892, Nov 2024. URL: https://doi.org/10.3390/biology13110892, doi:10.3390/biology13110892. This article has 16 citations.

  3. (ceccarelli2011carnitinepalmitoyltransferase(cpt) pages 1-3): Simona M. Ceccarelli, Odile Chomienne, Marcel Gubler, and Arduino Arduini. Carnitine palmitoyltransferase (cpt) modulators: a medicinal chemistry perspective on 35 years of research. Journal of medicinal chemistry, 54 9:3109-52, Apr 2011. URL: https://doi.org/10.1021/jm100809g, doi:10.1021/jm100809g. This article has 128 citations and is from a highest quality peer-reviewed journal.

  4. (duan2024theroleof pages 4-5): Yanxia Duan, Jiaxin Liu, Ailin Li, Chang Liu, Guang Shu, and Gang Yin. The role of the cpt family in cancer: searching for new therapeutic strategies. Biology, 13:892, Nov 2024. URL: https://doi.org/10.3390/biology13110892, doi:10.3390/biology13110892. This article has 16 citations.

  5. (volpicella2025carnitineoacetyltransferaseas pages 8-9): Mariateresa Volpicella, Maria Noemi Sgobba, Luna Laera, Anna Lucia Francavilla, Danila Imperia De Luca, Lorenzo Guerra, Ciro Leonardo Pierri, and Anna De Grassi. Carnitine o-acetyltransferase as a central player in lipid and branched-chain amino acid metabolism, epigenetics, cell plasticity, and organelle function. Biomolecules, 15:216, Feb 2025. URL: https://doi.org/10.3390/biom15020216, doi:10.3390/biom15020216. This article has 21 citations.

  6. (baker2024cpt2deficiencymodeled pages 4-5): Carly E. Baker, Aaron G. Marta, Nathan D. Zimmerman, Zeljka Korade, Nicholas W. Mathy, Delaney Wilton, Timothy Simeone, Andrew Kochvar, Kenneth L. Kramer, Holly A. F. Stessman, and Annemarie Shibata. Cpt2 deficiency modeled in zebrafish: abnormal neural development, electrical activity, behavior, and schizophrenia-related gene expression. Biomolecules, 14:914, Jul 2024. URL: https://doi.org/10.3390/biom14080914, doi:10.3390/biom14080914. This article has 1 citations.

  7. (baker2024cpt2deficiencymodeled pages 8-10): Carly E. Baker, Aaron G. Marta, Nathan D. Zimmerman, Zeljka Korade, Nicholas W. Mathy, Delaney Wilton, Timothy Simeone, Andrew Kochvar, Kenneth L. Kramer, Holly A. F. Stessman, and Annemarie Shibata. Cpt2 deficiency modeled in zebrafish: abnormal neural development, electrical activity, behavior, and schizophrenia-related gene expression. Biomolecules, 14:914, Jul 2024. URL: https://doi.org/10.3390/biom14080914, doi:10.3390/biom14080914. This article has 1 citations.

  8. (baker2024cpt2deficiencymodeled pages 1-2): Carly E. Baker, Aaron G. Marta, Nathan D. Zimmerman, Zeljka Korade, Nicholas W. Mathy, Delaney Wilton, Timothy Simeone, Andrew Kochvar, Kenneth L. Kramer, Holly A. F. Stessman, and Annemarie Shibata. Cpt2 deficiency modeled in zebrafish: abnormal neural development, electrical activity, behavior, and schizophrenia-related gene expression. Biomolecules, 14:914, Jul 2024. URL: https://doi.org/10.3390/biom14080914, doi:10.3390/biom14080914. This article has 1 citations.

  9. (baker2024cpt2deficiencymodeled pages 25-26): Carly E. Baker, Aaron G. Marta, Nathan D. Zimmerman, Zeljka Korade, Nicholas W. Mathy, Delaney Wilton, Timothy Simeone, Andrew Kochvar, Kenneth L. Kramer, Holly A. F. Stessman, and Annemarie Shibata. Cpt2 deficiency modeled in zebrafish: abnormal neural development, electrical activity, behavior, and schizophrenia-related gene expression. Biomolecules, 14:914, Jul 2024. URL: https://doi.org/10.3390/biom14080914, doi:10.3390/biom14080914. This article has 1 citations.

  10. (baker2024cpt2deficiencymodeled media c22cb2e6): Carly E. Baker, Aaron G. Marta, Nathan D. Zimmerman, Zeljka Korade, Nicholas W. Mathy, Delaney Wilton, Timothy Simeone, Andrew Kochvar, Kenneth L. Kramer, Holly A. F. Stessman, and Annemarie Shibata. Cpt2 deficiency modeled in zebrafish: abnormal neural development, electrical activity, behavior, and schizophrenia-related gene expression. Biomolecules, 14:914, Jul 2024. URL: https://doi.org/10.3390/biom14080914, doi:10.3390/biom14080914. This article has 1 citations.

  11. (nolen2024insilicobiomarker pages 8-9): Rayna M. Nolen, Lene H. Petersen, Karl Kaiser, Antonietta Quigg, and David Hala. In silico biomarker analysis of the adverse effects of perfluorooctane sulfonate (pfos) exposure on the metabolic physiology of embryo-larval zebrafish. Frontiers in Systems Biology, Mar 2024. URL: https://doi.org/10.3389/fsysb.2024.1367562, doi:10.3389/fsysb.2024.1367562. This article has 4 citations.

  12. (li2017systemicregulationof pages 2-4): Jia-Min Li, Ling-Yu Li, Xuan Qin, Li-Jun Ning, Dong-Liang Lu, Dong-Liang Li, Mei-Ling Zhang, Xin Wang, and Zhen-Yu Du. Systemic regulation of l-carnitine in nutritional metabolism in zebrafish, danio rerio. Scientific Reports, Jan 2017. URL: https://doi.org/10.1038/srep40815, doi:10.1038/srep40815. This article has 93 citations and is from a peer-reviewed journal.

  13. (yao2023mitochondrialcarnitinepalmitoyltransferaseii pages 2-4): Min Yao, Ping Zhou, Yan-Yan Qin, Li Wang, and Dengbing Yao. Mitochondrial carnitine palmitoyltransferase-ii dysfunction: a possible novel mechanism for nonalcoholic fatty liver disease in hepatocarcinogenesis. World Journal of Gastroenterology, 29:1765-1778, Mar 2023. URL: https://doi.org/10.3748/wjg.v29.i12.1765, doi:10.3748/wjg.v29.i12.1765. This article has 14 citations.

  14. (ceccarelli2011carnitinepalmitoyltransferase(cpt) pages 3-4): Simona M. Ceccarelli, Odile Chomienne, Marcel Gubler, and Arduino Arduini. Carnitine palmitoyltransferase (cpt) modulators: a medicinal chemistry perspective on 35 years of research. Journal of medicinal chemistry, 54 9:3109-52, Apr 2011. URL: https://doi.org/10.1021/jm100809g, doi:10.1021/jm100809g. This article has 128 citations and is from a highest quality peer-reviewed journal.

  15. (volpicella2025carnitineoacetyltransferaseas pages 9-11): Mariateresa Volpicella, Maria Noemi Sgobba, Luna Laera, Anna Lucia Francavilla, Danila Imperia De Luca, Lorenzo Guerra, Ciro Leonardo Pierri, and Anna De Grassi. Carnitine o-acetyltransferase as a central player in lipid and branched-chain amino acid metabolism, epigenetics, cell plasticity, and organelle function. Biomolecules, 15:216, Feb 2025. URL: https://doi.org/10.3390/biom15020216, doi:10.3390/biom15020216. This article has 21 citations.

  16. (li2017systemicregulationof pages 1-2): Jia-Min Li, Ling-Yu Li, Xuan Qin, Li-Jun Ning, Dong-Liang Lu, Dong-Liang Li, Mei-Ling Zhang, Xin Wang, and Zhen-Yu Du. Systemic regulation of l-carnitine in nutritional metabolism in zebrafish, danio rerio. Scientific Reports, Jan 2017. URL: https://doi.org/10.1038/srep40815, doi:10.1038/srep40815. This article has 93 citations and is from a peer-reviewed journal.

  17. (li2017systemicregulationof pages 6-7): Jia-Min Li, Ling-Yu Li, Xuan Qin, Li-Jun Ning, Dong-Liang Lu, Dong-Liang Li, Mei-Ling Zhang, Xin Wang, and Zhen-Yu Du. Systemic regulation of l-carnitine in nutritional metabolism in zebrafish, danio rerio. Scientific Reports, Jan 2017. URL: https://doi.org/10.1038/srep40815, doi:10.1038/srep40815. This article has 93 citations and is from a peer-reviewed journal.

Artifacts

Citations

  1. duan2024theroleof pages 2-4
  2. duan2024theroleof pages 4-5
  3. volpicella2025carnitineoacetyltransferaseas pages 8-9
  4. nolen2024insilicobiomarker pages 8-9
  5. li2017systemicregulationof pages 2-4
  6. yao2023mitochondrialcarnitinepalmitoyltransferaseii pages 2-4
  7. volpicella2025carnitineoacetyltransferaseas pages 9-11
  8. li2017systemicregulationof pages 1-2
  9. li2017systemicregulationof pages 6-7
  10. https://doi.org/10.3390/biom14080914
  11. https://doi.org/10.3390/biology13110892
  12. https://doi.org/10.3748/wjg.v29.i12.1765
  13. https://doi.org/10.1021/jm100809g
  14. https://doi.org/10.3390/biom15020216
  15. https://doi.org/10.3389/fsysb.2024.1367562
  16. https://doi.org/10.1038/srep40815
  17. https://doi.org/10.3390/biom14080914,
  18. https://doi.org/10.3390/biology13110892,
  19. https://doi.org/10.1021/jm100809g,
  20. https://doi.org/10.3390/biom15020216,
  21. https://doi.org/10.3389/fsysb.2024.1367562,
  22. https://doi.org/10.1038/srep40815,
  23. https://doi.org/10.3748/wjg.v29.i12.1765,

📚 Additional Documentation

Notes

(cpt2-notes.md)

cpt2 notes

2026-05-09 review notes

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.

📄 View Raw YAML

 
id: Q5U3U3
gene_symbol: cpt2
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:7955
  label: Danio rerio
description: 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.
existing_annotations:
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Mitochondrion localization is correct but less specific than mitochondrial inner membrane.
    additional_reference_ids:
    - file:DANRE/cpt2/cpt2-deep-research-falcon.md
    - PMID:39199302
    supported_by:
    - reference_id: file:DANRE/cpt2/cpt2-uniprot.txt
      supporting_text: 'FUNCTION: Involved in the intramitochondrial synthesis of acyl-CoAs for beta-oxidation from long-chain acylcarnitines.'
    - reference_id: file:DANRE/cpt2/cpt2-deep-research-falcon.md
      supporting_text: |-
        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).
      reference_section_type: RESULTS
    - reference_id: PMID:39199302
      supporting_text: |-
        A representative Western blot of CPT2 protein levels isolated from the mitochondrial fraction
      reference_section_type: RESULTS
- term:
    id: GO:0004095
    label: carnitine O-palmitoyltransferase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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.
    action: ACCEPT
    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.'
    additional_reference_ids:
    - file:DANRE/cpt2/cpt2-deep-research-falcon.md
    - PMID:39199302
    supported_by:
    - reference_id: file:DANRE/cpt2/cpt2-uniprot.txt
      supporting_text: 'FUNCTION: Involved in the intramitochondrial synthesis of acyl-CoAs for beta-oxidation from long-chain acylcarnitines.'
    - reference_id: file:DANRE/cpt2/cpt2-deep-research-falcon.md
      supporting_text: |-
        **CPT2’s core biochemical role** is to **reconvert fatty acylcarnitines to fatty acyl-CoA** at/near the **inner mitochondrial membrane**, releasing free carnitine for recycling.
      reference_section_type: RESULTS
    - reference_id: PMID:39199302
      supporting_text: |-
        carnitine palmitoyltransferase 2 (CPT2) that converts the long-chain acylcarnitine to acyl-CoA for oxidation in the inner mitochondrial membrane.
      reference_section_type: INTRODUCTION
- term:
    id: GO:0006635
    label: fatty acid beta-oxidation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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).
    action: ACCEPT
    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.'
    additional_reference_ids:
    - file:DANRE/cpt2/cpt2-deep-research-falcon.md
    - PMID:39199302
    supported_by:
    - reference_id: file:DANRE/cpt2/cpt2-uniprot.txt
      supporting_text: 'FUNCTION: Involved in the intramitochondrial synthesis of acyl-CoAs for beta-oxidation from long-chain acylcarnitines.'
    - reference_id: file:DANRE/cpt2/cpt2-deep-research-falcon.md
      supporting_text: |-
        LC-MS/MS profiling demonstrated significant increases in long-chain fatty-acylcarnitines in knockdown larvae.
      reference_section_type: RESULTS
    - reference_id: file:DANRE/cpt2/cpt2-deep-research-falcon.md
      supporting_text: |-
        consistent with a block at the CPT2 step (i.e., impaired reconversion of acylcarnitines to acyl-CoA for β-oxidation)
      reference_section_type: RESULTS
- term:
    id: GO:0004095
    label: carnitine O-palmitoyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    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).
    action: ACCEPT
    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.'
    additional_reference_ids:
    - file:DANRE/cpt2/cpt2-deep-research-falcon.md
    supported_by:
    - reference_id: file:DANRE/cpt2/cpt2-uniprot.txt
      supporting_text: 'FUNCTION: Involved in the intramitochondrial synthesis of acyl-CoAs for beta-oxidation from long-chain acylcarnitines.'
    - reference_id: file:DANRE/cpt2/cpt2-deep-research-falcon.md
      supporting_text: |-
        CPT1/CPT2 are specific for **long-chain fatty acyl-CoAs, reported as C8–C18**, 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.
      reference_section_type: DISCUSSION
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    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.
    action: ACCEPT
    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.'
    additional_reference_ids:
    - file:DANRE/cpt2/cpt2-deep-research-falcon.md
    - PMID:39199302
    supported_by:
    - reference_id: file:DANRE/cpt2/cpt2-uniprot.txt
      supporting_text: 'FUNCTION: Involved in the intramitochondrial synthesis of acyl-CoAs for beta-oxidation from long-chain acylcarnitines.'
    - reference_id: file:DANRE/cpt2/cpt2-deep-research-falcon.md
      supporting_text: |-
        CPT2 is consistently placed at the **inner mitochondrial membrane** and described as more **matrix-facing / matrix-protein-like** than CPT1.
      reference_section_type: DISCUSSION
    - reference_id: PMID:39199302
      supporting_text: |-
        carnitine palmitoyltransferase 2 (CPT2) that converts the long-chain acylcarnitine to acyl-CoA for oxidation in the inner mitochondrial membrane.
      reference_section_type: INTRODUCTION
- term:
    id: GO:0008458
    label: carnitine O-octanoyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Carnitine O-octanoyltransferase activity is supported as an acyl-chain variant activity, but palmitoyltransferase activity captures the canonical CPT2 role.
    additional_reference_ids:
    - file:DANRE/cpt2/cpt2-deep-research-falcon.md
    supported_by:
    - reference_id: file:DANRE/cpt2/cpt2-uniprot.txt
      supporting_text: 'FUNCTION: Involved in the intramitochondrial synthesis of acyl-CoAs for beta-oxidation from long-chain acylcarnitines.'
    - reference_id: file:DANRE/cpt2/cpt2-deep-research-falcon.md
      supporting_text: |-
        CPT2 is catalytically active on **mid-length and long-chain acyl-CoA esters**, but “virtually no activity” is observed on **short-chain** and **ultralong-chain** acyl-CoAs
      reference_section_type: DISCUSSION
- term:
    id: GO:0015909
    label: long-chain fatty acid transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids:
    - file:DANRE/cpt2/cpt2-deep-research-falcon.md
    supported_by:
    - reference_id: file:DANRE/cpt2/cpt2-uniprot.txt
      supporting_text: 'FUNCTION: Involved in the intramitochondrial synthesis of acyl-CoAs for beta-oxidation from long-chain acylcarnitines.'
    - reference_id: file:DANRE/cpt2/cpt2-deep-research-falcon.md
      supporting_text: |-
        CPT1 converts fatty acyl-CoA to acylcarnitine, CACT transports it, and **CPT2 “uncouples” it back to fatty acyl-CoA + L-carnitine at the inner mitochondrial membrane**, enabling entry into β-oxidation.
      reference_section_type: DISCUSSION
- term:
    id: GO:0016746
    label: acyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    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.
    action: MODIFY
    reason: The broad term is true but under-informative. The specific supported term for cpt2 is carnitine O-palmitoyltransferase activity.
    proposed_replacement_terms:
    - id: GO:0004095
      label: carnitine O-palmitoyltransferase activity
    additional_reference_ids:
    - file:DANRE/cpt2/cpt2-deep-research-falcon.md
    supported_by:
    - reference_id: file:DANRE/cpt2/cpt2-uniprot.txt
      supporting_text: 'FUNCTION: Involved in the intramitochondrial synthesis of acyl-CoAs for beta-oxidation from long-chain acylcarnitines.'
    - reference_id: file:DANRE/cpt2/cpt2-deep-research-falcon.md
      supporting_text: |-
        CPT1/CPT2 are specific for **long-chain fatty acyl-CoAs, reported as C8–C18**
      reference_section_type: DISCUSSION
- term:
    id: GO:0006635
    label: fatty acid beta-oxidation
  evidence_type: IEA
  original_reference_id: GO_REF:0000041
  review:
    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.
    action: ACCEPT
    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.'
    additional_reference_ids:
    - file:DANRE/cpt2/cpt2-deep-research-falcon.md
    supported_by:
    - reference_id: file:DANRE/cpt2/cpt2-uniprot.txt
      supporting_text: 'FUNCTION: Involved in the intramitochondrial synthesis of acyl-CoAs for beta-oxidation from long-chain acylcarnitines.'
    - reference_id: file:DANRE/cpt2/cpt2-deep-research-falcon.md
      supporting_text: |-
        Long-chain fatty acids (LCFAs) are oxidized in the **mitochondrial matrix** via β-oxidation
      reference_section_type: DISCUSSION
- term:
    id: GO:0004095
    label: carnitine O-palmitoyltransferase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    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.
    action: ACCEPT
    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.'
    additional_reference_ids:
    - file:DANRE/cpt2/cpt2-deep-research-falcon.md
    - PMID:39199302
    supported_by:
    - reference_id: file:DANRE/cpt2/cpt2-uniprot.txt
      supporting_text: 'FUNCTION: Involved in the intramitochondrial synthesis of acyl-CoAs for beta-oxidation from long-chain acylcarnitines.'
    - reference_id: file:DANRE/cpt2/cpt2-deep-research-falcon.md
      supporting_text: |-
        reports **~70.9% sequence homology** between zebrafish cpt2 and human CPT2, supporting that “cpt2” in zebrafish refers to the same conserved enzyme class as the UniProt record.
      reference_section_type: RESULTS
    - reference_id: PMID:39199302
      supporting_text: |-
        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).
      reference_section_type: INTRODUCTION
- term:
    id: GO:0008458
    label: carnitine O-octanoyltransferase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Carnitine O-octanoyltransferase activity is supported as an acyl-chain variant activity, but palmitoyltransferase activity captures the canonical CPT2 role.
    additional_reference_ids:
    - file:DANRE/cpt2/cpt2-deep-research-falcon.md
    supported_by:
    - reference_id: file:DANRE/cpt2/cpt2-uniprot.txt
      supporting_text: 'FUNCTION: Involved in the intramitochondrial synthesis of acyl-CoAs for beta-oxidation from long-chain acylcarnitines.'
    - reference_id: file:DANRE/cpt2/cpt2-deep-research-falcon.md
      supporting_text: |-
        A 2024 review summarizes that CPT2 is catalytically active on **mid-length and long-chain acyl-CoA esters**, but “virtually no activity” is observed on **short-chain** and **ultralong-chain** acyl-CoAs
      reference_section_type: DISCUSSION
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000041
  title: Gene Ontology annotation based on UniPathway vocabulary mapping
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: GO_REF:0000116
  title: Automatic Gene Ontology annotation based on Rhea mapping
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: file:DANRE/cpt2/cpt2-uniprot.txt
  title: UniProtKB entry Q5U3U3 for Danio rerio cpt2
  findings:
  - statement: 'FUNCTION: Involved in the intramitochondrial synthesis of acyl-CoAs for beta-oxidation from long-chain acylcarnitines.'
    supporting_text: 'FUNCTION: Involved in the intramitochondrial synthesis of acyl-CoAs for beta-oxidation from long-chain acylcarnitines.'
- id: file:DANRE/cpt2/cpt2-deep-research-falcon.md
  title: Falcon deep research report on Danio rerio cpt2 (Q5U3U3)
  findings:
  - statement: |
      Zebrafish cpt2 is the Danio rerio ortholog of human CPT2 (~70.9% sequence
      homology) and encodes a mitochondrial carnitine O-palmitoyltransferase 2 that
      reconverts long-chain acylcarnitines to acyl-CoA at the inner mitochondrial
      membrane as part of the carnitine shuttle, enabling long-chain fatty acid
      beta-oxidation.
    supporting_text: |-
      Independent zebrafish experimental work explicitly targets zebrafish **cpt2** as the ortholog of human CPT2 and reports **~70.9% sequence homology** between zebrafish cpt2 and human CPT2, supporting that “cpt2” in zebrafish refers to the same conserved enzyme class as the UniProt record.
    reference_section_type: RESULTS
  - statement: |
      The core biochemical role of CPT2 is to reconvert fatty acylcarnitines to fatty
      acyl-CoA at/near the inner mitochondrial membrane, releasing free carnitine for
      recycling; CPT1 makes acylcarnitine, CACT transports it, and CPT2 uncouples it
      back to acyl-CoA + L-carnitine for matrix beta-oxidation.
    supporting_text: |-
      **CPT2’s core biochemical role** is to **reconvert fatty acylcarnitines to fatty acyl-CoA** at/near the **inner mitochondrial membrane**, releasing free carnitine for recycling. A recent review describes the sequential steps: CPT1 converts fatty acyl-CoA to acylcarnitine, CACT transports it, and **CPT2 “uncouples” it back to fatty acyl-CoA + L-carnitine at the inner mitochondrial membrane**, enabling entry into β-oxidation.
    reference_section_type: DISCUSSION
  - statement: |
      CPT2 is catalytically active on mid-length and long-chain acyl-CoA esters (C8-C18)
      with virtually no activity on short-chain or ultralong-chain substrates,
      consistent with its canonical role in long-chain fatty acid oxidation.
    supporting_text: |-
      A 2024 review summarizes that CPT2 is catalytically active on **mid-length and long-chain acyl-CoA esters**, but “virtually no activity” is observed on **short-chain** and **ultralong-chain** acyl-CoAs (and some non-fatty-acyl substrates), which is consistent with CPT2’s canonical role in LCFA oxidation rather than short-chain metabolism.
    reference_section_type: DISCUSSION
  - statement: |
      In zebrafish, CPT2 protein was detected by Western blot in mitochondrial fractions
      from larvae, providing direct evidence that the cpt2 gene product localizes to
      mitochondria.
    supporting_text: |-
      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).
    reference_section_type: RESULTS
  - statement: |
      Morpholino knockdown of zebrafish cpt2 caused significant accumulation of
      long-chain fatty-acylcarnitines, the expected metabolic consequence of a block at
      the CPT2 step (impaired reconversion of acylcarnitines to acyl-CoA for
      beta-oxidation).
    supporting_text: |-
      LC-MS/MS profiling demonstrated significant increases in long-chain fatty-acylcarnitines in knockdown larvae. Total acylcarnitines increased by approximately **~70% (translation-blocking; p<0.001)** and **~42% (splice-blocking; p≤0.05)** versus wild-type, consistent with a block at the CPT2 step (i.e., impaired reconversion of acylcarnitines to acyl-CoA for β-oxidation).
    reference_section_type: RESULTS
- id: PMID:39199302
  title: 'Cpt2 Deficiency Modeled in Zebrafish: Abnormal Neural Development, Electrical
    Activity, Behavior, and Schizophrenia-Related Gene Expression'
  findings:
  - statement: |
      Zebrafish cpt2 and human CPT2 are orthologous, sharing 70.9% sequence alignment,
      supporting use of zebrafish as a model for CPT2 function.
    supporting_text: |-
      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).
    reference_section_type: INTRODUCTION
  - statement: |
      CPT2 is an inner mitochondrial membrane enzyme of the carnitine shuttle that
      converts long-chain acylcarnitine to acyl-CoA for beta-oxidation.
    supporting_text: |-
      carnitine palmitoyltransferase 2 (CPT2) that converts the long-chain acylcarnitine to acyl-CoA for oxidation in the inner mitochondrial membrane.
    reference_section_type: INTRODUCTION
  - statement: |
      Zebrafish CPT2 protein was detected in isolated mitochondrial fractions from
      larvae by Western blot, confirming mitochondrial localization.
    supporting_text: |-
      A representative Western blot of CPT2 protein levels isolated from the mitochondrial fraction
    reference_section_type: RESULTS
core_functions:
- description: cpt2 performs carnitine O-palmitoyltransferase activity as carnitine O-palmitoyltransferase 2, with activity localized primarily to mitochondrial inner membrane and directly supporting mitochondrial fatty acid beta-oxidation by regenerating acyl-CoAs from long-chain acylcarnitines.
  molecular_function:
    id: GO:0004095
    label: carnitine O-palmitoyltransferase activity
  directly_involved_in:
  - id: GO:0006635
    label: fatty acid beta-oxidation
  locations:
  - id: GO:0005743
    label: mitochondrial inner membrane
  supported_by:
  - reference_id: file:DANRE/cpt2/cpt2-uniprot.txt
    supporting_text: 'FUNCTION: Involved in the intramitochondrial synthesis of acyl-CoAs for beta-oxidation from long-chain acylcarnitines.'
  - reference_id: file:DANRE/cpt2/cpt2-deep-research-falcon.md
    supporting_text: |-
      **CPT2’s core biochemical role** is to **reconvert fatty acylcarnitines to fatty acyl-CoA** at/near the **inner mitochondrial membrane**, releasing free carnitine for recycling.
  - reference_id: PMID:39199302
    supporting_text: |-
      carnitine palmitoyltransferase 2 (CPT2) that converts the long-chain acylcarnitine to acyl-CoA for oxidation in the inner mitochondrial membrane.