GO:0106262 1-acylglycerophosphoethanolamine O-acyltransferase activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0106262 describes the enzymatic activity that converts a 1-acyl-sn-glycero-3-phosphoethanolamine into a 1,2-diacyl-sn-glycero-3-phosphoethanolamine using an acyl-CoA donor.
• This activity is part of the Kennedy pathway for phosphatidylethanolamine biosynthesis and contributes to membrane lipid remodeling.
• MBOAT2 is a membrane-bound O-acyltransferase that can exhibit this activity and has been linked to lipid metabolism reprogramming in intrahepatic cholangiocarcinoma.
• Circular RNA derived from MBOAT2 (circMBOAT2) promotes cancer progression by stabilizing PTBP1 and facilitating FASN mRNA export.
• Plasma levels of circMBOAT2 change with cardiac endurance training, suggesting a role in systemic lipid adaptation.
• Experimental dissection of GO:0106262 benefits from CRISPR knockout, point-mutation, knock-in, and overexpression models combined with lipidomics and RNA-seq.
Description
GO:0106262, 1-acylglycerophosphoethanolamine O-acyltransferase activity, is a molecular function that catalyzes the acylation of 1-acyl-sn-glycero-3-phosphoethanolamine to form 1,2-diacyl-sn-glycero-3-phosphoethanolamine, using acyl-CoA as the acyl donor. This reaction is a late step in the Kennedy pathway for phosphatidylethanolamine synthesis and is also relevant to membrane phospholipid remodeling. Researchers study this activity because phosphatidylethanolamine is a major membrane phospholipid and its acyl chain composition influences membrane curvature, protein trafficking, and signaling. The enzyme MBOAT2 has been associated with this activity and with cancer lipid metabolism reprogramming. Beyond cancer, circular RNA from MBOAT2 is detectable in plasma and changes with cardiac endurance training, indicating that this locus responds to physiological stress. Understanding GO:0106262 therefore connects basic lipid biochemistry to disease mechanisms and exercise physiology.
1-acylglycerophosphoethanolamine O-acyltransferase activity At A Glance
| GO ID | GO:0106262 |
|---|---|
| GO term | 1-acylglycerophosphoethanolamine O-acyltransferase activity |
| Ontology | molecular_function |
| Synonym | None listed in QuickGO |
| Major function | Acylates 1-acyl-sn-glycero-3-phosphoethanolamine to form 1,2-diacyl-sn-glycero-3-phosphoethanolamine using acyl-CoA |
| Reaction direction | Forward acylation with release of CoA |
| Representative enzyme | MBOAT2 (membrane-bound O-acyltransferase domain-containing 2) |
| Pathway context | Kennedy pathway / phosphatidylethanolamine biosynthesis and remodeling |
| Disease relevance | Lipid metabolism reprogramming in intrahepatic cholangiocarcinoma |
What Is GO:0106262?
GO:0106262 is defined as the catalysis of the reaction: a 1-acyl-sn-glycero-3-phosphoethanolamine + an acyl-CoA = a 1,2-diacyl-sn-glycero-3-phosphoethanolamine + CoA. In other words, it transfers an acyl group from acyl-CoA to the free hydroxyl at the sn-2 position of 1-acyl-glycerophosphoethanolamine, producing a diacylated phosphatidylethanolamine and releasing coenzyme A. This activity belongs to the molecular_function ontology and is one of the acyltransferase steps that determine the acyl chain composition of phosphatidylethanolamine.
Why Is 1-acylglycerophosphoethanolamine O-acyltransferase activity Important in Cell Biology?
GO:0106262 is important because it controls the final acylation step that gives phosphatidylethanolamine its mature acyl composition, which in turn affects membrane fluidity, curvature, and the recruitment of peripheral proteins. Dysregulation of this activity can support cancer cell proliferation by reprogramming lipid metabolism, as shown for MBOAT2 in intrahepatic cholangiocarcinoma. The same locus produces circular RNA whose plasma levels respond to endurance training, linking this enzymatic activity to systemic metabolic adaptation. Thus, GO:0106262 sits at the interface of membrane biogenesis, cancer biology, and exercise physiology.
• Provides the terminal acylation step for phosphatidylethanolamine synthesis via the Kennedy pathway.
• Determines the sn-2 acyl composition of phosphatidylethanolamine, influencing membrane properties.
• Supports lipid droplet and membrane expansion in rapidly proliferating cancer cells.
• Contributes to lipid metabolism reprogramming in intrahepatic cholangiocarcinoma.
• Is encoded by MBOAT2, a gene that also produces circular RNA detectable in plasma.
• CircMBOAT2 levels change with cardiac endurance training, suggesting physiological regulation.
• Offers a target for studying phosphatidylethanolamine homeostasis in metabolic disease.
• Can be interrogated with CRISPR knockout and lipidomics to separate enzymatic from non-enzymatic functions.
What Happens During 1-acylglycerophosphoethanolamine O-acyltransferase activity?
Substrate recognition and binding
In simple terms: The enzyme first grabs its two starting materials: a lysophospholipid and an activated fatty acid.
The reaction begins when the enzyme binds 1-acyl-sn-glycero-3-phosphoethanolamine and an acyl-CoA thioester. The lysophospholipid provides the glycerol backbone with a free sn-2 hydroxyl, while acyl-CoA supplies the fatty acid in an activated form. This binding step positions the substrates for efficient acyl transfer and is a key point of substrate selectivity.
Acyl transfer and product formation
In simple terms: The enzyme moves the fatty acid from CoA onto the lysophospholipid, making a fully acylated phosphatidylethanolamine.
Catalysis proceeds by transferring the acyl group from acyl-CoA to the sn-2 hydroxyl of 1-acyl-sn-glycero-3-phosphoethanolamine, yielding 1,2-diacyl-sn-glycero-3-phosphoethanolamine and free coenzyme A. This step completes the Kennedy pathway acylation and generates the mature diacylated phospholipid. The reaction is thought to occur at the membrane interface, where both substrates partition into the lipid bilayer.
Membrane integration and lipid remodeling
In simple terms: The new phospholipid joins the membrane and can be further remodeled.
The 1,2-diacyl-sn-glycero-3-phosphoethanolamine produced by GO:0106262 is inserted into cellular membranes and can undergo further acyl chain remodeling. In cancer cells, this activity supports the expanded membrane and lipid droplet requirements of rapid proliferation. MBOAT2-dependent lipid metabolism reprogramming has been observed in intrahepatic cholangiocarcinoma, where it contributes to disease progression.
Physiological modulation
In simple terms: The activity can change with exercise and other physiological states.
Plasma profiles of circular RNA MBOAT2 are altered by cardiac endurance training, indicating that the MBOAT2 locus responds to physiological demand. This suggests that GO:0106262-related lipid synthesis may be tuned to support membrane adaptation in exercised muscle and heart. The exact mechanisms linking training to MBOAT2 expression remain an active area of research.
Key Genes Involved in GO:0106262 1-acylglycerophosphoethanolamine O-acyltransferase activity
The following genes and proteins are directly or indirectly connected to GO:0106262, 1-acylglycerophosphoethanolamine O-acyltransferase activity, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| MBOAT2 | Membrane-bound O-acyltransferase that can catalyze GO:0106262 | Lipid metabolism reprogramming in intrahepatic cholangiocarcinoma |
| PTBP1 | RNA-binding protein stabilized by circMBOAT2 | Facilitates FASN mRNA cytoplasmic export in cancer |
| FASN | Fatty acid synthase | Target of circMBOAT2-PTBP1 axis in lipid metabolism |
| MBOAT1 | Related membrane-bound O-acyltransferase | Potential paralog with overlapping acyltransferase functions |
| MBOAT4 | Related membrane-bound O-acyltransferase | Family member for comparative studies |
| MBOAT7 | Lysophosphatidylinositol acyltransferase | Related acyltransferase for pathway context |
| AGPAT1 | 1-acylglycerol-3-phosphate O-acyltransferase | Kennedy pathway enzyme for comparison |
| AGPAT2 | 1-acylglycerol-3-phosphate O-acyltransferase | Kennedy pathway enzyme for comparison |
| LPCAT1 | Lysophosphatidylcholine acyltransferase | Related lysophospholipid acyltransferase |
| LPCAT3 | Lysophosphatidylcholine acyltransferase | Related lysophospholipid acyltransferase |
| LPEAT1 | Lysophosphatidylethanolamine acyltransferase | Plant homolog for comparative enzymology |
| LPEAT2 | Lysophosphatidylethanolamine acyltransferase | Plant homolog for comparative enzymology |
| GPAT1 | Glycerol-3-phosphate O-acyltransferase | Upstream Kennedy pathway enzyme |
| GPAT2 | Glycerol-3-phosphate O-acyltransferase | Upstream Kennedy pathway enzyme |
| CEPT1 | Choline/ethanolamine phosphotransferase | Generates phosphatidylethanolamine precursor |
| SLC1A5 | Glutamine transporter | Supports lipid synthesis in cancer metabolism |
| ACACA | Acetyl-CoA carboxylase | Provides malonyl-CoA for fatty acid synthesis |
How Is 1-acylglycerophosphoethanolamine O-acyltransferase activity Regulated?
Regulation of GO:0106262 is not fully defined, but published evidence links the MBOAT2 locus to cancer lipid metabolism and physiological exercise adaptation. In intrahepatic cholangiocarcinoma, circMBOAT2 promotes lipid metabolism reprogramming by stabilizing PTBP1 and facilitating FASN mRNA cytoplasmic export, indirectly supporting the lipid environment in which MBOAT2 acts. Cardiac endurance training alters plasma profiles of circular RNA MBOAT2, suggesting that systemic metabolic state can influence MBOAT2-related processes. These findings indicate that GO:0106262 may be regulated at the level of MBOAT2 expression and through interactions with RNA-binding proteins and fatty acid synthesis pathways.
1-acylglycerophosphoethanolamine O-acyltransferase activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| MBOAT2 | Intrahepatic cholangiocarcinoma | CRISPR knockout in cholangiocarcinoma cell lines followed by lipidomics |
| MBOAT2 | Cardiac endurance training response | Overexpression and knockout in cardiomyocytes with exercise mimetics |
| PTBP1 | Cancer lipid metabolism | Knockdown or knockout to test circMBOAT2-PTBP1 axis |
| FASN | Lipid synthesis in cancer | Point mutation or knockout to dissect FASN mRNA export |
| MBOAT2 | Phosphatidylethanolamine homeostasis | Knock-in of tagged MBOAT2 for localization and interaction studies |
Intrahepatic cholangiocarcinoma
Circular RNA MBOAT2 promotes intrahepatic cholangiocarcinoma progression and lipid metabolism reprogramming by stabilizing PTBP1 to facilitate FASN mRNA cytoplasmic export. This links the MBOAT2 locus, and by extension GO:0106262-related acyltransferase activity, to cancer lipid metabolism and tumor progression. The study highlights MBOAT2 as a potential target in cholangiocarcinoma research.
Cardiac adaptation and exercise physiology
Cardiac endurance training alters plasma profiles of circular RNA MBOAT2, indicating that the MBOAT2 locus responds to physiological stress. This suggests that GO:0106262-related lipid synthesis may participate in membrane remodeling during cardiac adaptation. The finding also supports circMBOAT2 as a potential biomarker for exercise response.
Lipid metabolism disorders
Because GO:0106262 contributes to phosphatidylethanolamine synthesis and remodeling, its dysregulation could affect membrane lipid composition in metabolic disorders. MBOAT2-dependent lipid metabolism reprogramming in cancer provides a proof of concept that this activity can be co-opted in disease. Further studies are needed to define its role in obesity, diabetes, and cardiovascular disease.
From 1-acylglycerophosphoethanolamine O-acyltransferase activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of MBOAT2 reduce GO:0106262 activity? | CRISPR knockout of MBOAT2 in cancer cell lines |
| Which acyl-CoA species are preferred? | Point mutation of predicted catalytic residues followed by enzyme assays |
| Where does MBOAT2 localize in cells? | Knock-in of fluorescent or epitope tag at the endogenous locus |
| Does MBOAT2 overexpression reprogram lipid metabolism? | Doxycycline-inducible overexpression in cancer cells |
| Does circMBOAT2 affect PTBP1 and FASN? | Overexpression of circMBOAT2 or knockdown of PTBP1 |
| Does exercise change MBOAT2-related lipids? | In vivo exercise models with plasma circRNA profiling |
How to Study the 1-acylglycerophosphoethanolamine O-acyltransferase activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Lipidomics | Phosphatidylethanolamine species and acyl composition | Assess GO:0106262 activity in cells |
| In vitro acyltransferase assay | Conversion of lysophospholipid to diacyl phospholipid | Direct enzymatic characterization |
| RNA-seq | MBOAT2 mRNA and circMBOAT2 expression | Link genotype to lipid metabolism |
| Circular RNA profiling | Plasma circMBOAT2 levels | Exercise response biomarker |
| Proteomics | MBOAT2 interaction partners | Identify regulators of GO:0106262 |
| Fluorescence imaging | Subcellular localization of MBOAT2 | Determine membrane compartment of activity |
| CRISPR screening | Genes required for lipid metabolism | Discover modifiers of GO:0106262 |
| qPCR | Transcript levels of MBOAT2 and FASN | Validate circMBOAT2-PTBP1 axis |
Lipidomics and enzyme assays
Lipidomics can quantify 1-acyl-sn-glycero-3-phosphoethanolamine and 1,2-diacyl-sn-glycero-3-phosphoethanolamine levels to infer GO:0106262 activity in cells. In vitro acyltransferase assays using acyl-CoA donors and lysophospholipid acceptors can directly measure the reaction. These methods are essential for linking MBOAT2 genotype to enzymatic phenotype.
RNA-seq and circular RNA profiling
RNA-seq can measure MBOAT2 mRNA and circMBOAT2 levels, which are relevant to lipid metabolism reprogramming. Circular RNA profiling in plasma has been used to detect changes in circMBOAT2 after cardiac endurance training. These approaches connect GO:0106262-related gene expression to physiological and disease states.
Proteomics and interactomics
Proteomics can identify proteins that co-purify with MBOAT2 and may regulate its acyltransferase activity. The interaction between circMBOAT2 and PTBP1 was identified through molecular biology approaches, illustrating how interactomics can reveal non-enzymatic functions of the locus. Such studies help separate GO:0106262 catalysis from RNA-mediated roles.
Imaging and subcellular localization
Fluorescence imaging of tagged MBOAT2 can reveal its distribution among the endoplasmic reticulum, lipid droplets, and other membranes. Localization is important because GO:0106262 acts at membrane interfaces where substrates partition. Imaging can also show how lipid droplets change upon MBOAT2 perturbation.
How CRISPR Can Be Used to Study GO:0106262 1-acylglycerophosphoethanolamine O-acyltransferase activity
Knockout
CRISPR knockout of MBOAT2 can eliminate GO:0106262 activity in cells, allowing researchers to test its contribution to phosphatidylethanolamine synthesis and cancer lipid metabolism. Knockout models are useful for lipidomics and proliferation assays in intrahepatic cholangiocarcinoma cell lines. They also help distinguish enzymatic from circular RNA functions of the MBOAT2 locus.
Point Mutation
Point mutation of predicted catalytic residues in MBOAT2 can dissect the acyltransferase mechanism of GO:0106262. Such mutants can be expressed in knockout backgrounds to test whether enzymatic activity is required for lipid metabolism reprogramming. This approach is valuable for separating catalysis from protein-protein interactions.
Knock-in
Knock-in of epitope or fluorescent tags at the endogenous MBOAT2 locus enables localization and interaction studies under native regulation. Tagged knock-in can also be used to immunoprecipitate MBOAT2 and identify associated lipids or proteins. This is important for understanding where GO:0106262 acts within the cell.
Overexpression
Overexpression of MBOAT2 or circMBOAT2 can amplify GO:0106262-related phenotypes and reveal downstream effects such as PTBP1 stabilization and FASN mRNA export. Inducible overexpression systems allow time-controlled lipid metabolism reprogramming studies. Overexpression in cardiomyocytes or exercise models can test physiological adaptation.
How EDITGENE Supports 1-acylglycerophosphoethanolamine O-acyltransferase activity Research
Researchers studying 1-acylglycerophosphoethanolamine O-acyltransferase activity-related genes often need to determine whether a candidate gene is causally involved in phosphatidylethanolamine synthesis, cancer lipid metabolism, or physiological adaptation. EDITGENE provides CRISPR-based cell model services that enable precise genetic perturbations for such mechanistic studies.
Contact EDITGENE today to design your custom CRISPR model for 1-acylglycerophosphoethanolamine O-acyltransferase activity research.
Frequently Asked Questions About 1-acylglycerophosphoethanolamine O-acyltransferase activity
What is GO:0106262?
GO:0106262 is the Gene Ontology molecular function term for 1-acylglycerophosphoethanolamine O-acyltransferase activity, which catalyzes the acylation of 1-acyl-sn-glycero-3-phosphoethanolamine to form 1,2-diacyl-sn-glycero-3-phosphoethanolamine using acyl-CoA.
What reaction does 1-acylglycerophosphoethanolamine O-acyltransferase activity catalyze?
It transfers an acyl group from acyl-CoA to the sn-2 hydroxyl of 1-acyl-sn-glycero-3-phosphoethanolamine, producing 1,2-diacyl-sn-glycero-3-phosphoethanolamine and CoA.
Which gene encodes an enzyme with this activity?
MBOAT2 is a membrane-bound O-acyltransferase that can exhibit this activity and has been studied in cancer lipid metabolism.
What is the role of MBOAT2 in cancer?
Circular RNA MBOAT2 promotes intrahepatic cholangiocarcinoma progression and lipid metabolism reprogramming by stabilizing PTBP1 to facilitate FASN mRNA cytoplasmic export.
Is MBOAT2 related to exercise?
Cardiac endurance training alters plasma profiles of circular RNA MBOAT2, suggesting a physiological response.
What pathways use GO:0106262?
It is part of the Kennedy pathway for phosphatidylethanolamine biosynthesis and membrane lipid remodeling.
How can I study GO:0106262 in the lab?
CRISPR knockout, point mutation, knock-in, overexpression, lipidomics, RNA-seq, and circular RNA profiling are common approaches.
What diseases are linked to this activity?
Intrahepatic cholangiocarcinoma is linked through MBOAT2 and circMBOAT2, while cardiac adaptation is linked through exercise-responsive circMBOAT2.
What is the substrate of 1-acylglycerophosphoethanolamine O-acyltransferase?
The substrates are 1-acyl-sn-glycero-3-phosphoethanolamine and an acyl-CoA.
What are the products of GO:0106262?
The products are 1,2-diacyl-sn-glycero-3-phosphoethanolamine and coenzyme A.
Conclusion
GO:0106262, 1-acylglycerophosphoethanolamine O-acyltransferase activity, is a defined molecular function that completes the acylation of phosphatidylethanolamine in the Kennedy pathway. Its representative enzyme MBOAT2 has been implicated in intrahepatic cholangiocarcinoma lipid metabolism reprogramming and in physiological responses to cardiac endurance training. Studying this activity with CRISPR models and lipidomics will clarify how phosphatidylethanolamine composition contributes to cancer and metabolic adaptation.
References
- 1. Yu X et al.. 2023. CircRNA MBOAT2 promotes intrahepatic cholangiocarcinoma progression and lipid metabolism reprogramming by stabilizing PTBP1 to facilitate FASN mRNA cytoplasmic export.. Cell Death Dis 14(1):20 PMID: 36635270
- 2. Meinecke A et al.. 2020. Cardiac endurance training alters plasma profiles of circular RNA MBOAT2.. Am J Physiol Heart Circ Physiol 319(1):H13-H21 PMID: 32412780
