LPCAT2

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0003841 1-acylglycerol-3-phosphate O-acyltransferase activity	IDA PMID:20363836 Enzymatic activity of the human 1-acylglycerol-3-phosphate-O...	ACCEPT	Summary: LPCAT2 has been experimentally demonstrated to have AGPAT activity, converting lysophosphatidic acid (LPA) to phosphatidic acid (PA) by acylating at the sn-2 position. Agarwal and Garg (2010) showed that LPCAT2/AGPAT11 expressed in HEK-293 cells has AGPAT activity but lacks GPAT activity. The enzyme efficiently uses C18:1 LPA as acyl acceptor. Reason: This annotation is directly supported by experimental evidence in PMID:20363836. AGPAT activity is a verified enzymatic function of LPCAT2 (EC 2.3.1.51). Supporting Evidence: PMID:20363836 In vitro enzymatic activity using lysates of Human Embryonic Kidney-293 cells infected with recombinant AGPAT11/LPCAT2/lyso platelet-activating factor-acetyltransferase cDNA adenovirus show that the protein has an AGPAT activity but lacks glycerol-3-phosphate acyltransferase enzymatic activity. file:human/LPCAT2/LPCAT2-deep-research-falcon.md See deep research file for comprehensive analysis
GO:0005789 endoplasmic reticulum membrane	IDA PMID:20363836 Enzymatic activity of the human 1-acylglycerol-3-phosphate-O...	ACCEPT	Summary: Agarwal and Garg (2010) demonstrated that when LPCAT2 cDNA was expressed in CHO and HeLa cells, the protein product localized to the endoplasmic reticulum. Reason: ER membrane localization is directly experimentally verified by PMID:20363836 and confirmed by PMID:21498505. This represents the primary subcellular location of LPCAT2. Supporting Evidence: PMID:20363836 When AGPAT11/LPCAT2/lyso platelet-activating factor acetyltransferase cDNA was expressed in CHO and HeLa cells, the protein product localized to the endoplasmic reticulum.
GO:0005783 endoplasmic reticulum	IDA PMID:21498505 Human lysophosphatidylcholine acyltransferases 1 and 2 are l...	ACCEPT	Summary: Moessinger et al. (2011) showed that LPCAT2 localizes to the ER, with 70-90% of the protein found in membrane fractions in sucrose gradient analysis. Reason: ER localization is well-established experimentally. This is the primary location where LPCAT2 performs its enzymatic functions. Supporting Evidence: PMID:21498505 were reported to localize to the endoplasmic reticulum and to function in lung surfactant production and in inflammation response
GO:0005811 lipid droplet	IDA PMID:21498505 Human lysophosphatidylcholine acyltransferases 1 and 2 are l...	ACCEPT	Summary: Moessinger et al. (2011) demonstrated that 10-30% of endogenous LPCAT2 floated with lipid droplet fractions on sucrose gradients, with the remainder in membrane fractions. The monotopic topology of LPCAT2 enables this dual ER/LD localization. Reason: Lipid droplet localization is experimentally verified and represents a secondary but functionally important location where LPCAT2 catalyzes local PC synthesis. Supporting Evidence: PMID:21498505 we show in various mammalian cell lines that both enzymes additionally localize to lipid droplets (LDs), which consist of a core of neutral lipids surrounded by a monolayer of phospholipid, mainly PC
GO:0036151 phosphatidylcholine acyl-chain remodeling	IDA PMID:21498505 Human lysophosphatidylcholine acyltransferases 1 and 2 are l...	ACCEPT	Summary: Moessinger et al. (2011) demonstrated that LPCAT2 catalyzes the conversion of lysophosphatidylcholine (lysoPC) to phosphatidylcholine (PC), which is the reacylation step of the Lands cycle for PC acyl-chain remodeling. Reason: PC acyl-chain remodeling (Lands cycle) is a core biological process for LPCAT2, directly supported by experimental evidence. Supporting Evidence: PMID:21498505 The recently identified key enzymes of the Lands cycle, lysophosphatidylcholine acyltransferase 1 and 2 (LPCAT1 and -2), were reported to localize to the endoplasmic reticulum
GO:0047184 1-acylglycerophosphocholine O-acyltransferase activity	IDA PMID:21498505 Human lysophosphatidylcholine acyltransferases 1 and 2 are l...	ACCEPT	Summary: LPCAT2's primary enzymatic activity as a lysophosphatidylcholine acyltransferase (EC 2.3.1.23) was directly demonstrated by Moessinger et al. (2011), showing conversion of lysoPC to PC using acyl-CoA donors. Reason: This is the primary molecular function of LPCAT2, directly demonstrated experimentally. The enzyme reacylates lysoPC at the sn-2 position in the Lands cycle. Supporting Evidence: PMID:21498505 Human lysophosphatidylcholine acyltransferases 1 and 2 are located in lipid droplets where they catalyze the formation of phosphatidylcholine
GO:0005783 endoplasmic reticulum	IDA GO_REF:0000052	ACCEPT	Summary: Human Protein Atlas immunofluorescence data confirms ER localization of LPCAT2, consistent with direct experimental evidence from primary literature. Reason: Confirms the well-established ER localization from multiple independent studies. Supporting Evidence: PMID:21498505 2011 Apr 15. Human lysophosphatidylcholine acyltransferases 1 and 2 are located in lipid droplets where they catalyze the formation of phosphatidylcholine. PMID:20363836 Enzymatic activity of the human 1-acylglycerol-3-phosphate-O-acyltransferase isoform 11: upregulated in breast and cervical cancers.
GO:0005811 lipid droplet	IDA GO_REF:0000052	ACCEPT	Summary: HPA immunofluorescence confirms lipid droplet localization, consistent with detailed subcellular fractionation studies from Moessinger et al. (2011). Reason: Lipid droplet localization is independently confirmed by multiple approaches. Supporting Evidence: PMID:21498505 2011 Apr 15. Human lysophosphatidylcholine acyltransferases 1 and 2 are located in lipid droplets where they catalyze the formation of phosphatidylcholine.
GO:0005783 endoplasmic reticulum	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic inference of ER localization is consistent with direct experimental evidence from multiple human studies showing LPCAT2 in the ER. Reason: IBA annotation aligns with IDA evidence; ER is the primary localization. Supporting Evidence: PMID:21498505 2011 Apr 15. Human lysophosphatidylcholine acyltransferases 1 and 2 are located in lipid droplets where they catalyze the formation of phosphatidylcholine. PMID:20363836 Enzymatic activity of the human 1-acylglycerol-3-phosphate-O-acyltransferase isoform 11: upregulated in breast and cervical cancers.
GO:0042171 lysophosphatidic acid acyltransferase activity	IBA GO_REF:0000033	ACCEPT	Summary: LPCAT2 has verified AGPAT activity (LPA acyltransferase), converting LPA to PA. This is experimentally demonstrated and phylogenetically conserved. Reason: AGPAT/LPAAT activity is a verified enzymatic function of LPCAT2 (EC 2.3.1.51), demonstrated in PMID:20363836. Supporting Evidence: PMID:20363836 The protein has an AGPAT activity... The AGPAT11 efficiently uses C18:1 LPA as acyl acceptor and C18:1 fatty acid as an acyl donor.
GO:0036151 phosphatidylcholine acyl-chain remodeling	TAS Reactome:R-HSA-1482788	ACCEPT	Summary: Reactome pathway annotation for PC acyl chain remodeling is consistent with LPCAT2's role in the Lands cycle. Reason: PC remodeling via the Lands cycle is a core function of LPCAT2, supported by primary literature. Supporting Evidence: PMID:21498505 2011 Apr 15. Human lysophosphatidylcholine acyltransferases 1 and 2 are located in lipid droplets where they catalyze the formation of phosphatidylcholine.
GO:0003841 1-acylglycerol-3-phosphate O-acyltransferase activity	TAS Reactome:R-HSA-1482547	ACCEPT	Summary: Reactome annotation for AGPAT activity is consistent with experimental evidence demonstrating LPCAT2's ability to acylate LPA at sn-1. Reason: AGPAT activity is experimentally verified for LPCAT2. Supporting Evidence: PMID:20363836 Enzymatic activity of the human 1-acylglycerol-3-phosphate-O-acyltransferase isoform 11: upregulated in breast and cervical cancers.
GO:0047144 2-acylglycerol-3-phosphate O-acyltransferase activity	TAS Reactome:R-HSA-1482533	KEEP AS NON CORE	Summary: This annotation suggests LPCAT2 can acylate 2-acyl-sn-glycero-3-phosphate (sn-1 acylation). While LPCAT2 primarily acylates at sn-2 position, this represents a less well-characterized activity. Reason: LPCAT2 primarily functions as an sn-2 acyltransferase. This activity is less well-characterized than the primary AGPAT activity at sn-2. Retaining as Reactome has curated this pathway.
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-1482533	ACCEPT	Summary: ER membrane localization is consistent with experimental evidence. Reason: ER membrane is the primary location, well-supported by IDA evidence.
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-1482547	ACCEPT	Summary: Duplicate ER membrane annotation from different Reactome reaction. Reason: ER membrane localization is well-established.
GO:0005783 endoplasmic reticulum	ISS GO_REF:0000024	ACCEPT	Summary: ISS annotation based on mouse ortholog Q8BYI6. ER localization is confirmed by direct human experimental data. Reason: ER localization is confirmed by IDA in human cells.
GO:0005795 Golgi stack	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Golgi localization inferred from mouse ortholog. UniProt mentions Golgi apparatus membrane by similarity. Less well-established than ER localization. Reason: Golgi localization is supported by similarity evidence but not as strongly established as ER/lipid droplet localization by direct human experimental data.
GO:0006663 platelet activating factor biosynthetic process	ISS GO_REF:0000024	ACCEPT	Summary: PAF biosynthesis is a core function of LPCAT2, which has lyso-PAF acetyltransferase activity (EC 2.3.1.67). The enzyme catalyzes conversion of lyso-PAF to PAF using acetyl-CoA, especially in inflammatory cells. Reason: PAF biosynthesis is a verified core function of LPCAT2. The enzyme is distinguished from LPCAT1 by its inducible lyso-PAF acetyltransferase activity in inflammatory cells, analogous to COX-2.
GO:0047184 1-acylglycerophosphocholine O-acyltransferase activity	ISS GO_REF:0000024	ACCEPT	Summary: LPCAT activity inferred from mouse ortholog is confirmed by direct human experimental data (EC 2.3.1.23). Reason: This is the primary molecular function of LPCAT2, confirmed by IDA.
GO:0047192 1-alkylglycerophosphocholine O-acetyltransferase activity	ISS GO_REF:0000024	ACCEPT	Summary: Lyso-PAF acetyltransferase activity (EC 2.3.1.67) is a core function of LPCAT2, enabling PAF biosynthesis. This inducible activity distinguishes LPCAT2 from LPCAT1. Reason: Lyso-PAF acetyltransferase activity is a verified core function of LPCAT2, directly linked to its role in inflammatory PAF biosynthesis.
GO:0061024 membrane organization	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: LPCAT2's role in PC synthesis contributes to membrane organization and lipid droplet biogenesis. The enzyme regulates lipid droplet number and size. Reason: Membrane organization is a downstream consequence of LPCAT2's lipid remodeling activity rather than its primary function. Keep as non-core. Supporting Evidence: PMID:21498505 LDs have the ability to locally synthesize PC and that this activity correlates with the LPCAT1 and -2 expression level.
GO:0000139 Golgi membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Golgi membrane localization is annotated based on UniProt subcellular location. UniProt notes Golgi apparatus membrane by similarity to mouse. Reason: Golgi localization is less well-established than ER/lipid droplet localization. Keep as a secondary location annotation.
GO:0003841 1-acylglycerol-3-phosphate O-acyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: AGPAT activity is correctly annotated based on EC number 2.3.1.51. Reason: AGPAT activity is experimentally verified.
GO:0005509 calcium ion binding	IEA GO_REF:0000002	ACCEPT	Summary: LPCAT2 contains EF-hand domains (IPR002048) that bind calcium. The enzyme's activity is Ca2+-dependent, distinguishing it from LPCAT1. Reason: Calcium binding via EF-hand domains is structurally predicted and functionally relevant - LPCAT2's activity is Ca2+-dependent.
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: ER membrane localization from UniProt subcellular location is consistent with experimental evidence. Reason: ER membrane is the primary location, confirmed by IDA.
GO:0005811 lipid droplet	IEA GO_REF:0000044	ACCEPT	Summary: Lipid droplet localization from UniProt is confirmed by experimental data. Reason: Lipid droplet localization is experimentally verified in PMID:21498505.
GO:0005886 plasma membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Plasma membrane localization is annotated by similarity to mouse ortholog in UniProt, but is not strongly supported by direct human experimental evidence. Reason: Plasma membrane localization is noted by similarity in UniProt but is not as well-established as ER/lipid droplet localization.
GO:0006629 lipid metabolic process	IEA GO_REF:0000043	MARK AS OVER ANNOTATED	Summary: LPCAT2 is indeed involved in lipid metabolism, but this is a very general term. Reason: This is too general. More specific terms like "phosphatidylcholine acyl-chain remodeling" (GO:0036151) and "platelet activating factor biosynthetic process" (GO:0006663) better describe LPCAT2's functions.
GO:0006650 glycerophospholipid metabolic process	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: LPCAT2 is involved in glycerophospholipid metabolism, specifically PC and PAF biosynthesis. This is more specific than lipid metabolic process but still broad. Reason: While accurate, more specific terms better describe LPCAT2's role. Keep as a broader context annotation.
GO:0008374 O-acyltransferase activity	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: O-acyltransferase activity is correct but generic. LPCAT2 has specific LPCAT and AGPAT activities. Reason: This is a parent term of the more specific acyltransferase activities that LPCAT2 possesses. The specific activities are more informative.
GO:0008654 phospholipid biosynthetic process	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: LPCAT2 contributes to phospholipid biosynthesis through PC remodeling and PA synthesis, but this is a broad term. Reason: Accurate but broad. More specific terms like PC acyl-chain remodeling better describe the function.
GO:0016740 transferase activity	IEA GO_REF:0000043	MARK AS OVER ANNOTATED	Summary: Transferase activity is far too general for LPCAT2. Reason: This is a very high-level MF term that provides minimal information. The specific acyltransferase activities are much more informative.
GO:0016746 acyltransferase activity	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	Summary: Acyltransferase activity is correct but still quite general. Reason: LPCAT2 has specific acyltransferase activities (LPCAT, AGPAT, lyso-PAF acetyltransferase) that are more informative than this parent term.
GO:0031984 organelle subcompartment	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: This is an extremely generic cellular component term. Reason: Too generic. LPCAT2 has specific localizations (ER membrane, lipid droplet) that are much more informative.
GO:0042171 lysophosphatidic acid acyltransferase activity	IEA GO_REF:0000117	ACCEPT	Summary: LPAAT/AGPAT activity is a verified function of LPCAT2 based on EC 2.3.1.51. Reason: This activity is experimentally demonstrated in PMID:20363836.
GO:0046872 metal ion binding	IEA GO_REF:0000043	MODIFY	Summary: LPCAT2 binds calcium via EF-hand domains. Reason: While correct, "calcium ion binding" (GO:0005509) is more specific and already annotated. This generic term should be replaced with the specific calcium binding. Proposed replacements: calcium ion binding
GO:0047159 plasmalogen synthase activity	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Plasmalogen synthase activity (EC 2.3.1.25) for LPCAT2 is based on similarity to mouse ortholog Q8BYI6 in UniProt. This is a less well-characterized activity. Reason: This activity is annotated by similarity in UniProt but lacks direct human experimental evidence. Keep as non-core pending verification.
GO:0047184 1-acylglycerophosphocholine O-acyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: LPCAT activity (EC 2.3.1.23) is a primary function experimentally verified. Reason: Core enzymatic function confirmed by IDA evidence.
GO:0047192 1-alkylglycerophosphocholine O-acetyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: Lyso-PAF acetyltransferase activity (EC 2.3.1.67) is a core function for PAF biosynthesis. Reason: This inducible acetyltransferase activity is central to LPCAT2's role in inflammation and PAF biosynthesis.
GO:0005783 endoplasmic reticulum	IEA GO_REF:0000120	ACCEPT	Summary: ER localization is consistent with experimental evidence. Reason: ER is the primary location, confirmed by IDA.
GO:0005795 Golgi stack	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Golgi localization from Ensembl Compara ortholog transfer. Reason: Secondary localization, less well-established than ER/lipid droplet.
GO:0006663 platelet activating factor biosynthetic process	IEA GO_REF:0000107	ACCEPT	Summary: PAF biosynthesis is a core function of LPCAT2 through its lyso-PAF acetyltransferase activity. Reason: This is a defining function of LPCAT2, distinguishing it from LPCAT1.
GO:0016020 membrane	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	Summary: Generic membrane localization. Reason: Too generic. LPCAT2 has specific membrane localizations (ER membrane, lipid droplet, Golgi membrane) that are more informative.
GO:0061024 membrane organization	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: LPCAT2 contributes to membrane organization through PC synthesis and lipid droplet regulation. Reason: This is a downstream effect of LPCAT2's lipid remodeling activity rather than its primary function.
GO:0006644 phospholipid metabolic process	IEA GO_REF:0000041	KEEP AS NON CORE	Summary: LPCAT2 is involved in phospholipid metabolism via the Lands cycle and PAF biosynthesis. Reason: Accurate but broad. More specific BP terms are available.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome	KEEP AS NON CORE	Summary: LPCAT2 was identified as interacting with several proteins (EBP, ERGIC3, HSD17B13, KCNJ6, MFSD14B, RETREG3, RHBDD1) in the HuRI human reference interactome study. These are high-throughput Y2H interactions. Reason: The "protein binding" term is uninformative and should generally be avoided. However, the interactions detected in this high-throughput study may be relevant to LPCAT2's function in the ER/lipid droplet. Keep as non-core pending more specific characterization of these interactions. Supporting Evidence: PMID:32296183 Apr 8. A reference map of the human binary protein interactome.

Core Functions

Inducible lyso-PAF acetyltransferase activity (EC 2.3.1.67) converting lyso-PAF to platelet-activating factor (PAF) using acetyl-CoA. This Ca2+-dependent, LPS-inducible activity distinguishes LPCAT2 from constitutive LPCAT1 (analogous to COX-2 vs COX-1). Upon inflammatory stimulation via TLR4/p38 MAPK pathway, the enzyme preferentially uses acetyl-CoA for PAF biosynthesis.

Molecular Function:

1-alkylglycerophosphocholine O-acetyltransferase activity

Directly Involved In:

platelet activating factor biosynthetic process

Cellular Locations:

endoplasmic reticulum membrane

Supporting Evidence:

PMID:17182612
The enzyme was induced by bacterial endotoxin (lipopolysaccharide), which was suppressed by dexamethasone treatment... Upon acute inflammatory stimulation with lipopolysaccharide, the activated enzyme utilizes acetyl-CoA more efficiently and produces PAF.

Lysophosphatidylcholine acyltransferase activity (EC 2.3.1.23) converting lysoPC to PC by incorporating acyl-CoA (including arachidonoyl-CoA) at the sn-2 position. This reacylation step of the Lands cycle maintains membrane phospholipid composition. Under resting conditions, LPCAT2 preferentially catalyzes this acyltransferase reaction over the acetyltransferase reaction, contributing to membrane biogenesis. LPCAT2 also functions on lipid droplets where it catalyzes local PC synthesis.

Molecular Function:

1-acylglycerophosphocholine O-acyltransferase activity

Directly Involved In:

phosphatidylcholine acyl-chain remodeling

Cellular Locations:

endoplasmic reticulum membrane lipid droplet

Supporting Evidence:

PMID:21498505
Human lysophosphatidylcholine acyltransferases 1 and 2 are located in lipid droplets where they catalyze the formation of phosphatidylcholine
PMID:17182612
Under resting conditions, the enzyme prefers arachidonoyl-CoA and contributes to membrane biogenesis.

AGPAT activity (EC 2.3.1.51) converting lysophosphatidic acid (LPA) to phosphatidic acid (PA) by acylation at the sn-2 position. Demonstrated using C18:1 LPA as acyl acceptor. This activity contributes to de novo phospholipid biosynthesis distinct from the Lands cycle remodeling pathway.

Molecular Function:

1-acylglycerol-3-phosphate O-acyltransferase activity

Cellular Locations:

endoplasmic reticulum membrane

Supporting Evidence:

PMID:20363836
In vitro enzymatic activity using lysates of Human Embryonic Kidney-293 cells infected with recombinant AGPAT11/LPCAT2/lyso platelet-activating factor-acetyltransferase cDNA adenovirus show that the protein has an AGPAT activity but lacks glycerol-3-phosphate acyltransferase enzymatic activity.

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:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping

GO_REF:0000052

Gene Ontology annotation based on curation of immunofluorescence data

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:17182612

A single enzyme catalyzes both platelet-activating factor production and membrane biogenesis of inflammatory cells. Cloning and characterization of acetyl-CoA:LYSO-PAF acetyltransferase.

LPCAT2 was cloned and characterized as an acetyl-CoA:lyso-PAF acetyltransferase

"A single enzyme catalyzes both platelet-activating factor production and membrane biogenesis of inflammatory cells. Cloning and characterization of acetyl-CoA:lyso-PAF acetyltransferase."
The enzyme catalyzes both PAF production and membrane PC synthesis

"Upon acute inflammatory stimulation with lipopolysaccharide, the activated enzyme utilizes acetyl-CoA more efficiently and produces PAF."
LPCAT2 is inducible in inflammatory cells

"The enzyme was induced by bacterial endotoxin (lipopolysaccharide), which was suppressed by dexamethasone treatment."

PMID:20363836

Enzymatic activity of the human 1-acylglycerol-3-phosphate-O-acyltransferase isoform 11: upregulated in breast and cervical cancers

LPCAT2/AGPAT11 has AGPAT activity (LPA to PA conversion)

"In vitro enzymatic activity using lysates of Human Embryonic Kidney-293 cells infected with recombinant AGPAT11/LPCAT2/lyso platelet-activating factor-acetyltransferase cDNA adenovirus show that the protein has an AGPAT activity but lacks glycerol-3-phosphate acyltransferase enzymatic activity."
Lacks GPAT activity

"the protein has an AGPAT activity but lacks glycerol-3-phosphate acyltransferase enzymatic activity."
Localizes to ER in CHO and HeLa cells

"When AGPAT11/LPCAT2/lyso platelet-activating factor acetyltransferase cDNA was expressed in CHO and HeLa cells, the protein product localized to the endoplasmic reticulum."
Upregulated in breast, cervical, and colorectal cancers

"Expression of AGPAT11 mRNA was significantly upregulated in human breast, cervical, and colorectal cancer tissues, indicating its adjuvant role in the progression of these cancers."

PMID:21498505

Human lysophosphatidylcholine acyltransferases 1 and 2 are located in lipid droplets where they catalyze the formation of phosphatidylcholine

LPCAT2 localizes to both ER and lipid droplets

"Here, we show in various mammalian cell lines that both enzymes additionally localize to lipid droplets (LDs), which consist of a core of neutral lipids surrounded by a monolayer of phospholipid, mainly PC."
LPCAT2 has dual ER and lipid droplet localization enabled by monotopic topology

"This dual localization is enabled by the monotopic topology of these enzymes demonstrated in this study."
Catalyzes local PC synthesis on lipid droplets

"Furthermore, we show that LDs have the ability to locally synthesize PC and that this activity correlates with the LPCAT1 and -2 expression level."

PMID:32296183

A reference map of the human binary protein interactome

High-throughput Y2H study identifying protein-protein interactions

Reactome:R-HSA-1482533

2-acyl LPC is acylated to PC by LPCAT

Reactome:R-HSA-1482547

1-acyl LPC is acylated to PC by LPCAT

Reactome:R-HSA-1482788

Acyl chain remodelling of PC

file:human/LPCAT2/LPCAT2-deep-research-falcon.md

Deep research on LPCAT2 function

Suggested Experiments

Experiment: Structural studies (cryo-EM or X-ray crystallography) of LPCAT2 with and without calcium to understand EF-hand domain regulation. Would elucidate the mechanism of Ca2+-dependent activation.

Experiment: Lipidomics analysis comparing PC species in cells with LPCAT2 knockdown versus LPCAT1 knockdown to define substrate preferences in vivo. Would clarify the distinct contributions of LPCAT1 and LPCAT2 to membrane PC composition.

Deep Research

Falcon

(LPCAT2-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 19 citations 2025-12-21T23:52:01.470584

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.

Plan (concise)
- Verify identity and nomenclature: LPCAT2 (UniProt Q7L5N7), human, aliases AGPAT11/AYTL1; LPCAT family with EF-hand–related annotations in UniProt. (Verification completed.)
- Compile recent primary studies/reviews (2023–2024) plus key mechanistic classics on enzymatic function, specificity, localization, and regulation; extract quantitative/statistical data. (Completed.)
- Map roles in biochemical pathways (Lands’ cycle; PAF biosynthesis; inflammatory lipid mediator/eicosanoid context) and disease-relevant mechanisms (cancer, immunity, differentiation). (Completed.)
- Synthesize current applications/analysis and expert perspectives. (Completed.)
- Write comprehensive, well-cited report with URLs and publication dates. (Completed.)

Comprehensive research report: Human LPCAT2 (UniProt Q7L5N7)

Identity verification and nomenclature
- Gene/protein: Lysophosphatidylcholine acyltransferase 2 (LPCAT2), synonyms AGPAT11, AYTL1; human enzyme in the LPCAT/LPLAT family. This matches the user-supplied UniProt identity and aliases. (wang2019phospholipidremodelingin pages 28-28, shindou2009recentprogresson pages 4-5)
- Organism: Homo sapiens. Mechanistic and localization data below include human experimental evidence; several classic functional insights derive from mouse macrophages but are conserved and widely cited. (wang2019phospholipidremodelingin pages 28-28, shindou2009recentprogresson pages 3-4)
- Family/domains: Member of AGPAT/LPLAT superfamily, often annotated with EF-hand–related motifs and regulatory Ca2+-responsiveness at the activity level. (shindou2009recentprogresson pages 4-5, shindou2009recentprogresson pages 3-4)

Key concepts and definitions (current understanding)
- Primary biochemical role: LPCAT2 is a lysophospholipid acyltransferase that reacylates lysophosphatidylcholine (lysoPC) at sn-2 using acyl‑CoA, contributing to Lands’ cycle phosphatidylcholine (PC) remodeling. It also functions as a lyso-PAF acetyltransferase (lysoPAFAT) that acetylates lyso‑PAF using acetyl‑CoA to generate platelet-activating factor (PAF), especially in inflammatory cells. This dual activity underlies its inducible role in inflammation versus constitutive membrane remodeling. (shindou2009recentprogresson pages 4-5, shindou2009recentprogresson pages 3-4, wang2019phospholipidremodelingin pages 28-28)
- Inducible vs constitutive paradigm: LPCAT2 is typically inducible/inflammatory, analogous to COX‑2, whereas LPCAT1 is constitutive, analogous to COX‑1. (shindou2009recentprogresson pages 4-5)

Enzymatic functions, reactions, and substrate specificity
- Reactions:
• LPLAT/LPCAT reaction: lysoPC + acyl‑CoA → PC + CoA‑SH (sn‑2 reacylation in Lands’ cycle). (shindou2009recentprogresson pages 4-5)
• Lyso‑PAF acetyltransferase: lyso‑PAF + acetyl‑CoA → PAF + CoA‑SH (inducible PAF biosynthesis in macrophages). (shindou2009recentprogresson pages 4-5, shindou2009recentprogresson pages 3-4, wang2019phospholipidremodelingin pages 28-28)
- Substrate specificity (evidence-based):
• LPC species: Acts on lysoPC within remodeling and on lyso‑PAF within PAF synthesis. (shindou2009recentprogresson pages 4-5, shindou2009recentprogresson pages 3-4)
• Acyl‑CoA preferences: Family literature emphasizes PUFA incorporation at sn‑2, including arachidonoyl‑CoA, though LPCAT isoform preferences vary; LPCAT2 has been reported as an LPLAT with lysoPC activity and inducible lyso‑PAF acetylation. Targeted 2024 differentiation studies assayed LPCAT activity with 16:0, 18:1, 18:2, 20:4 (arachidonoyl‑CoA), and 22:6 acyl‑CoAs in vitro, supporting use of common physiological acyl donors in cell systems. (tabe2024theroleof pages 3-5)
• Reviews summarizing LPCAT2 indicate lysoPC/lysoPS acceptance and potential preference for oleoyl‑CoA in some contexts; these are review-level inferences. (korbecki2024phospholipidacyltransferasescharacterization pages 8-9)

Subcellular localization and structural/biophysical features
- Localization: Human LPCAT2 localizes to the endoplasmic reticulum and to lipid droplets (LDs). In mammalian cells, 10–30% of total LPCAT2 floated with LD fractions in sucrose gradients, with the remainder in membranes; both LPCAT1/2 showed dual ER/LD localization. This supports local PC synthesis on LD surfaces. (moessinger2011humanlysophosphatidylcholineacyltransferases pages 3-5)
- Topology: LPCAT2 is a monotopic membrane protein with a long hydrophobic segment enabling insertion into the LD phospholipid monolayer. (moessinger2011humanlysophosphatidylcholineacyltransferases pages 3-5)

Regulation and domains
- Ca2+ dependence and signaling: LPCAT2 activity is Ca2+-dependent (contrasting LPCAT1), and its lyso‑PAF acetyltransferase activity is acutely activated by LPS via a p38 MAPK–dependent pathway in macrophages; dexamethasone suppresses LPS‑induced LPCAT2 mRNA upregulation. These findings establish LPCAT2 as an inducible inflammatory enzyme. (shindou2009recentprogresson pages 3-4)

Pathways and biochemical context
- Lands’ cycle (PC remodeling): LPCAT2 contributes to reacylation of lysoPC to remodel membrane PC composition at sn‑2, shaping membrane properties and lipid mediator pools. (shindou2009recentprogresson pages 4-5)
- PAF biosynthesis: In inflammatory cells, LPCAT2 catalyzes lyso‑PAF acetylation to form PAF, providing a mechanism to couple membrane remodeling and rapid bioactive lipid production during TLR4 stimulation. (shindou2009recentprogresson pages 3-4, wang2019phospholipidremodelingin pages 28-28)
- Downstream inflammatory lipid mediator milieu: Inducible PAF production via LPCAT2 interfaces with eicosanoid-producing pathways in activated immune cells, as part of broader inflammatory lipid remodeling. (shindou2009recentprogresson pages 4-5)

Recent developments (2023–2024) and latest research
- 2024—Osteoblastic differentiation: In C2C12 cells, LPCAT2 mRNA and protein increased during osteoblastic differentiation; siRNA knockdown of LPCAT2 reduced osteoblastic markers (e.g., ALP, Col1) and decreased lipid droplet number/size, with statistical significance (ANOVA/t‑test, P < 0.05). Activity assays evaluated incorporation from multiple acyl‑CoAs including arachidonoyl‑CoA. These data implicate LPCAT2 in BMP/Smad signaling and osteoblastogenesis via lipid remodeling. (Published Jul 2024; https://doi.org/10.1002/2211-5463.13845) (tabe2024theroleof pages 3-5)
- 2024—Broad acyltransferase review: A comprehensive 2024 review summarizes LPCAT/AGPAT roles in membrane remodeling and disease, noting LPCAT2’s associations with inflammation and cancer; it aggregates survival correlations across cancers and mechanistic links to LD biology. As a review, it synthesizes earlier primary literature and should be interpreted accordingly. (Published May 2024; https://doi.org/10.3390/cancers16112115) (korbecki2024phospholipidacyltransferasescharacterization pages 27-29, korbecki2024phospholipidacyltransferasescharacterization pages 8-9)

Current applications and real-world implementations
- Cancer lipid metabolism and chemoresistance: LPCAT2-driven lipid droplet biogenesis in colorectal cancer cells supports resistance to 5‑fluorouracil and oxaliplatin by dampening ER-stress–linked death pathways and limiting immunogenic cell death. Genetic manipulation of LPCAT2 modulates LD content and drug sensitivity in vitro and in mouse models, suggesting LPCAT2/LD-targeting strategies to resensitize tumors. (Published Jan 2018; https://doi.org/10.1038/s41467-017-02732-5) (wang2019phospholipidremodelingin pages 16-17)
- Immune/inflammatory signaling: In macrophage models, LPS acutely activates LPCAT2 lyso‑PAF acetyltransferase activity via p38 MAPK, linking TLR4 signaling to PAF production; dexamethasone suppresses LPS-induced LPCAT2 expression. These mechanistic axes connect LPCAT2 to real-world contexts like infection and sepsis biology. (Published Apr 2009; https://doi.org/10.1194/jlr.r800035-jlr200) (shindou2009recentprogresson pages 3-4)

Expert opinions and analysis
- Authoritative review perspective: LPCAT family enzymes, including LPCAT2, are central to phospholipid remodeling and pathophysiology; LPCAT2 is specifically highlighted in cancer contexts (chemoresistance, tumor progression) and in inducible inflammatory lipid mediator production, though mechanistic links to disease require further in vivo validation and selective chemical probes. (Published Feb 2019; https://doi.org/10.1146/annurev-physiol-020518-114444) (wang2019phospholipidremodelingin pages 16-17)

Relevant statistics and quantitative data
- Subcellular partitioning: In human cell lines, 10–30% of endogenous LPCAT2 floated with lipid droplet fractions on sucrose gradients, with the remainder in membrane/bottom fractions; both ER and LD localization are observed microscopically. (Published Jun 2011; https://doi.org/10.1074/jbc.M110.202424) (moessinger2011humanlysophosphatidylcholineacyltransferases pages 3-5)
- Differentiation model metrics: During C2C12 osteoblastic differentiation, ALP staining/activity increased by day 7 and LPCAT2 knockdown significantly reduced ALP and Col1 expression and decreased LD number/size (P < 0.05; multiple tests), implicating LPCAT2 functionally in osteoblastogenesis. (Published Jul 2024; https://doi.org/10.1002/2211-5463.13845) (tabe2024theroleof pages 3-5)

Disease associations and translational relevance (selected)
- Colorectal cancer: Elevated LPCAT2 associates with lipid droplet accumulation and chemoresistance; experimental modulation alters response to 5‑FU/oxaliplatin in vitro and in vivo, pointing to LPCAT2 as a druggable node in tumor lipid metabolism. (wang2019phospholipidremodelingin pages 16-17)
- Inflammation/innate immunity: TLR4–p38–LPCAT2 axis controls inducible PAF production; glucocorticoids suppress inducible expression, aligning LPCAT2 with anti-inflammatory pharmacology. (shindou2009recentprogresson pages 3-4)
- Differentiation and bone biology: LPCAT2 supports osteoblastic differentiation in C2C12 cells, potentially linking lipid remodeling, LD dynamics, and BMP/Smad signaling in osteogenesis. (tabe2024theroleof pages 3-5)

Limitations and open questions
- Isoform-specific substrate preferences and kinetics in human primary cells remain incompletely defined; detailed enzymology (kcat/Km by acyl‑CoA and lysoPC species) and structural basis for Ca2+ regulation merit updated investigation in 2023–2025 primary studies. (shindou2009recentprogresson pages 4-5, wang2019phospholipidremodelingin pages 16-17)
- Selective, in vivo–validated LPCAT2 inhibitors suitable for clinical translation are still needed to probe causality in inflammation and cancer.

Conclusion
Human LPCAT2 (Q7L5N7) is an inducible lysophospholipid acyltransferase at the ER and lipid droplets that couples Lands’ cycle PC remodeling with lyso‑PAF acetyltransferase activity for PAF biosynthesis. Its Ca2+‑dependent, p38‑MAPK–linked activation in macrophages anchors a role in inflammatory signaling, while its control of lipid droplet PC synthesis connects it to cancer chemoresistance and to differentiation programs sensitive to membrane lipid composition. Emerging 2024 data extend LPCAT2 biology to osteoblastic differentiation, underscoring LPCAT2 as a regulator of cell fate and stress responses through lipid remodeling. (shindou2009recentprogresson pages 3-4, wang2019phospholipidremodelingin pages 28-28, moessinger2011humanlysophosphatidylcholineacyltransferases pages 3-5, tabe2024theroleof pages 3-5, wang2019phospholipidremodelingin pages 16-17, shindou2009recentprogresson pages 4-5)

References

(wang2019phospholipidremodelingin pages 28-28): Bo Wang and Peter Tontonoz. Phospholipid remodeling in physiology and disease. Annual review of physiology, 81:165-188, Feb 2019. URL: https://doi.org/10.1146/annurev-physiol-020518-114444, doi:10.1146/annurev-physiol-020518-114444. This article has 481 citations and is from a highest quality peer-reviewed journal.
(shindou2009recentprogresson pages 4-5): Hideo Shindou, Daisuke Hishikawa, Takeshi Harayama, Koichi Yuki, and Takao Shimizu. Recent progress on acyl coa: lysophospholipid acyltransferase research. Journal of Lipid Research, 50:S46-S51, Apr 2009. URL: https://doi.org/10.1194/jlr.r800035-jlr200, doi:10.1194/jlr.r800035-jlr200. This article has 340 citations and is from a peer-reviewed journal.
(shindou2009recentprogresson pages 3-4): Hideo Shindou, Daisuke Hishikawa, Takeshi Harayama, Koichi Yuki, and Takao Shimizu. Recent progress on acyl coa: lysophospholipid acyltransferase research. Journal of Lipid Research, 50:S46-S51, Apr 2009. URL: https://doi.org/10.1194/jlr.r800035-jlr200, doi:10.1194/jlr.r800035-jlr200. This article has 340 citations and is from a peer-reviewed journal.
(tabe2024theroleof pages 3-5): Shirou Tabe, Hisako Hikiji, Tomomi Hashidate‐Yoshida, Hideo Shindou, Takao Shimizu, and Kazuhiro Tominaga. The role of lysophosphatidylcholine acyltransferase 2 in osteoblastic differentiation of c2c12 cells. FEBS Open Bio, 14:1490-1502, Jul 2024. URL: https://doi.org/10.1002/2211-5463.13845, doi:10.1002/2211-5463.13845. This article has 3 citations and is from a peer-reviewed journal.
(korbecki2024phospholipidacyltransferasescharacterization pages 8-9): Jan Korbecki, Mateusz Bosiacki, Maciej Pilarczyk, Magdalena Gąssowska-Dobrowolska, Paweł Jarmużek, Izabela Szućko-Kociuba, Justyna Kulik-Sajewicz, Dariusz Chlubek, and Irena Baranowska-Bosiacka. Phospholipid acyltransferases: characterization and involvement of the enzymes in metabolic and cancer diseases. Cancers, 16:2115, May 2024. URL: https://doi.org/10.3390/cancers16112115, doi:10.3390/cancers16112115. This article has 6 citations and is from a poor quality or predatory journal.
(moessinger2011humanlysophosphatidylcholineacyltransferases pages 3-5): Christine Moessinger, Lars Kuerschner, Johanna Spandl, Andrej Shevchenko, and Christoph Thiele. Human lysophosphatidylcholine acyltransferases 1 and 2 are located in lipid droplets where they catalyze the formation of phosphatidylcholine. Journal of Biological Chemistry, 286:21330-21339, Jun 2011. URL: https://doi.org/10.1074/jbc.m110.202424, doi:10.1074/jbc.m110.202424. This article has 198 citations and is from a domain leading peer-reviewed journal.
(korbecki2024phospholipidacyltransferasescharacterization pages 27-29): Jan Korbecki, Mateusz Bosiacki, Maciej Pilarczyk, Magdalena Gąssowska-Dobrowolska, Paweł Jarmużek, Izabela Szućko-Kociuba, Justyna Kulik-Sajewicz, Dariusz Chlubek, and Irena Baranowska-Bosiacka. Phospholipid acyltransferases: characterization and involvement of the enzymes in metabolic and cancer diseases. Cancers, 16:2115, May 2024. URL: https://doi.org/10.3390/cancers16112115, doi:10.3390/cancers16112115. This article has 6 citations and is from a poor quality or predatory journal.
(wang2019phospholipidremodelingin pages 16-17): Bo Wang and Peter Tontonoz. Phospholipid remodeling in physiology and disease. Annual review of physiology, 81:165-188, Feb 2019. URL: https://doi.org/10.1146/annurev-physiol-020518-114444, doi:10.1146/annurev-physiol-020518-114444. This article has 481 citations and is from a highest quality peer-reviewed journal.

Citations

shindou2009recentprogresson pages 4-5
tabe2024theroleof pages 3-5
korbecki2024phospholipidacyltransferasescharacterization pages 8-9
moessinger2011humanlysophosphatidylcholineacyltransferases pages 3-5
shindou2009recentprogresson pages 3-4
wang2019phospholipidremodelingin pages 16-17
wang2019phospholipidremodelingin pages 28-28
korbecki2024phospholipidacyltransferasescharacterization pages 27-29
https://doi.org/10.1002/2211-5463.13845
https://doi.org/10.3390/cancers16112115
https://doi.org/10.1038/s41467-017-02732-5
https://doi.org/10.1194/jlr.r800035-jlr200
https://doi.org/10.1146/annurev-physiol-020518-114444
https://doi.org/10.1074/jbc.M110.202424
https://doi.org/10.1146/annurev-physiol-020518-114444,
https://doi.org/10.1194/jlr.r800035-jlr200,
https://doi.org/10.1002/2211-5463.13845,
https://doi.org/10.3390/cancers16112115,
https://doi.org/10.1074/jbc.m110.202424,

📄 View Raw YAML

id: Q7L5N7
gene_symbol: LPCAT2
product_type: PROTEIN
aliases:
  - AGPAT11
  - AYTL1
  - LysoPAFAT
  - LPAAT-alpha
  - LPC acyltransferase 2
  - 1-AGPAT 11
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: 'LPCAT2 (Lysophosphatidylcholine acyltransferase 2) is an inducible membrane-bound
  enzyme with dual acyltransferase and acetyltransferase activities. It functions
  primarily in the Lands cycle for phosphatidylcholine (PC) remodeling and in the
  biosynthesis of platelet-activating factor (PAF). The enzyme catalyzes: (1) the
  conversion of lysophosphatidylcholine (lysoPC) to PC using acyl-CoA donors (EC 2.3.1.23);
  (2) the conversion of lysophosphatidic acid (LPA) to phosphatidic acid (PA) (EC
  2.3.1.51); (3) the acetylation of lyso-PAF to produce PAF using acetyl-CoA (EC 2.3.1.67);
  and (4) plasmalogen synthesis (EC 2.3.1.25). LPCAT2 is distinguished from LPCAT1
  by being inducible (analogous to COX-2 vs COX-1), Ca2+-dependent, and activated
  by LPS via p38 MAPK pathway in inflammatory cells. The enzyme localizes primarily
  to the ER membrane with 10-30% also found in lipid droplets where it contributes
  to local PC synthesis. Contains EF-hand domains for calcium binding and the conserved
  HXXXXD catalytic motif.'
existing_annotations:
  - term:
      id: GO:0003841
      label: 1-acylglycerol-3-phosphate O-acyltransferase activity
    evidence_type: IDA
    original_reference_id: PMID:20363836
    review:
      summary: LPCAT2 has been experimentally demonstrated to have AGPAT
        activity, converting lysophosphatidic acid (LPA) to phosphatidic acid
        (PA) by acylating at the sn-2 position. Agarwal and Garg (2010) showed
        that LPCAT2/AGPAT11 expressed in HEK-293 cells has AGPAT activity but
        lacks GPAT activity. The enzyme efficiently uses C18:1 LPA as acyl
        acceptor.
      action: ACCEPT
      reason: This annotation is directly supported by experimental evidence in
        PMID:20363836. AGPAT activity is a verified enzymatic function of LPCAT2
        (EC 2.3.1.51).
      supported_by:
        - reference_id: PMID:20363836
          supporting_text: In vitro enzymatic activity using lysates of Human
            Embryonic Kidney-293 cells infected with recombinant
            AGPAT11/LPCAT2/lyso platelet-activating factor-acetyltransferase
            cDNA adenovirus show that the protein has an AGPAT activity but
            lacks glycerol-3-phosphate acyltransferase enzymatic activity.
        - reference_id: file:human/LPCAT2/LPCAT2-deep-research-falcon.md
          supporting_text: See deep research file for comprehensive analysis
  - term:
      id: GO:0005789
      label: endoplasmic reticulum membrane
    evidence_type: IDA
    original_reference_id: PMID:20363836
    review:
      summary: Agarwal and Garg (2010) demonstrated that when LPCAT2 cDNA was
        expressed in CHO and HeLa cells, the protein product localized to the
        endoplasmic reticulum.
      action: ACCEPT
      reason: ER membrane localization is directly experimentally verified by
        PMID:20363836 and confirmed by PMID:21498505. This represents the
        primary subcellular location of LPCAT2.
      supported_by:
        - reference_id: PMID:20363836
          supporting_text: When AGPAT11/LPCAT2/lyso platelet-activating factor
            acetyltransferase cDNA was expressed in CHO and HeLa cells, the
            protein product localized to the endoplasmic reticulum.
  - term:
      id: GO:0005783
      label: endoplasmic reticulum
    evidence_type: IDA
    original_reference_id: PMID:21498505
    review:
      summary: Moessinger et al. (2011) showed that LPCAT2 localizes to the ER,
        with 70-90% of the protein found in membrane fractions in sucrose
        gradient analysis.
      action: ACCEPT
      reason: ER localization is well-established experimentally. This is the
        primary location where LPCAT2 performs its enzymatic functions.
      supported_by:
        - reference_id: PMID:21498505
          supporting_text: were reported to localize to the endoplasmic
            reticulum and to function in lung surfactant production and in
            inflammation response
  - term:
      id: GO:0005811
      label: lipid droplet
    evidence_type: IDA
    original_reference_id: PMID:21498505
    review:
      summary: Moessinger et al. (2011) demonstrated that 10-30% of endogenous
        LPCAT2 floated with lipid droplet fractions on sucrose gradients, with
        the remainder in membrane fractions. The monotopic topology of LPCAT2
        enables this dual ER/LD localization.
      action: ACCEPT
      reason: Lipid droplet localization is experimentally verified and
        represents a secondary but functionally important location where LPCAT2
        catalyzes local PC synthesis.
      supported_by:
        - reference_id: PMID:21498505
          supporting_text: we show in various mammalian cell lines that both
            enzymes additionally localize to lipid droplets (LDs), which consist
            of a core of neutral lipids surrounded by a monolayer of
            phospholipid, mainly PC
  - term:
      id: GO:0036151
      label: phosphatidylcholine acyl-chain remodeling
    evidence_type: IDA
    original_reference_id: PMID:21498505
    review:
      summary: Moessinger et al. (2011) demonstrated that LPCAT2 catalyzes the
        conversion of lysophosphatidylcholine (lysoPC) to phosphatidylcholine
        (PC), which is the reacylation step of the Lands cycle for PC acyl-chain
        remodeling.
      action: ACCEPT
      reason: PC acyl-chain remodeling (Lands cycle) is a core biological
        process for LPCAT2, directly supported by experimental evidence.
      supported_by:
        - reference_id: PMID:21498505
          supporting_text: The recently identified key enzymes of the Lands
            cycle, lysophosphatidylcholine acyltransferase 1 and 2 (LPCAT1 and
            -2), were reported to localize to the endoplasmic reticulum
  - term:
      id: GO:0047184
      label: 1-acylglycerophosphocholine O-acyltransferase activity
    evidence_type: IDA
    original_reference_id: PMID:21498505
    review:
      summary: LPCAT2's primary enzymatic activity as a lysophosphatidylcholine
        acyltransferase (EC 2.3.1.23) was directly demonstrated by Moessinger et
        al. (2011), showing conversion of lysoPC to PC using acyl-CoA donors.
      action: ACCEPT
      reason: This is the primary molecular function of LPCAT2, directly
        demonstrated experimentally. The enzyme reacylates lysoPC at the sn-2
        position in the Lands cycle.
      supported_by:
        - reference_id: PMID:21498505
          supporting_text: Human lysophosphatidylcholine acyltransferases 1 and
            2 are located in lipid droplets where they catalyze the formation of
            phosphatidylcholine
  - term:
      id: GO:0005783
      label: endoplasmic reticulum
    evidence_type: IDA
    original_reference_id: GO_REF:0000052
    review:
      summary: Human Protein Atlas immunofluorescence data confirms ER
        localization of LPCAT2, consistent with direct experimental evidence
        from primary literature.
      action: ACCEPT
      reason: Confirms the well-established ER localization from multiple
        independent studies.
      additional_reference_ids:
        - PMID:21498505
        - PMID:20363836
      supported_by:
        - reference_id: PMID:21498505
          supporting_text: 2011 Apr 15. Human lysophosphatidylcholine
            acyltransferases 1 and 2 are located in lipid droplets where they
            catalyze the formation of phosphatidylcholine.
        - reference_id: PMID:20363836
          supporting_text: 'Enzymatic activity of the human 1-acylglycerol-3-phosphate-O-acyltransferase
            isoform 11: upregulated in breast and cervical cancers.'
  - term:
      id: GO:0005811
      label: lipid droplet
    evidence_type: IDA
    original_reference_id: GO_REF:0000052
    review:
      summary: HPA immunofluorescence confirms lipid droplet localization,
        consistent with detailed subcellular fractionation studies from
        Moessinger et al. (2011).
      action: ACCEPT
      reason: Lipid droplet localization is independently confirmed by multiple
        approaches.
      additional_reference_ids:
        - PMID:21498505
      supported_by:
        - reference_id: PMID:21498505
          supporting_text: 2011 Apr 15. Human lysophosphatidylcholine
            acyltransferases 1 and 2 are located in lipid droplets where they
            catalyze the formation of phosphatidylcholine.
  - term:
      id: GO:0005783
      label: endoplasmic reticulum
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: Phylogenetic inference of ER localization is consistent with
        direct experimental evidence from multiple human studies showing LPCAT2
        in the ER.
      action: ACCEPT
      reason: IBA annotation aligns with IDA evidence; ER is the primary
        localization.
      additional_reference_ids:
        - PMID:21498505
        - PMID:20363836
      supported_by:
        - reference_id: PMID:21498505
          supporting_text: 2011 Apr 15. Human lysophosphatidylcholine
            acyltransferases 1 and 2 are located in lipid droplets where they
            catalyze the formation of phosphatidylcholine.
        - reference_id: PMID:20363836
          supporting_text: 'Enzymatic activity of the human 1-acylglycerol-3-phosphate-O-acyltransferase
            isoform 11: upregulated in breast and cervical cancers.'
  - term:
      id: GO:0042171
      label: lysophosphatidic acid acyltransferase activity
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: LPCAT2 has verified AGPAT activity (LPA acyltransferase),
        converting LPA to PA. This is experimentally demonstrated and
        phylogenetically conserved.
      action: ACCEPT
      reason: AGPAT/LPAAT activity is a verified enzymatic function of LPCAT2
        (EC 2.3.1.51), demonstrated in PMID:20363836.
      supported_by:
        - reference_id: PMID:20363836
          supporting_text: The protein has an AGPAT activity... The AGPAT11
            efficiently uses C18:1 LPA as acyl acceptor and C18:1 fatty acid as
            an acyl donor.
  - term:
      id: GO:0036151
      label: phosphatidylcholine acyl-chain remodeling
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1482788
    review:
      summary: Reactome pathway annotation for PC acyl chain remodeling is
        consistent with LPCAT2's role in the Lands cycle.
      action: ACCEPT
      reason: PC remodeling via the Lands cycle is a core function of LPCAT2,
        supported by primary literature.
      additional_reference_ids:
        - PMID:21498505
      supported_by:
        - reference_id: PMID:21498505
          supporting_text: 2011 Apr 15. Human lysophosphatidylcholine
            acyltransferases 1 and 2 are located in lipid droplets where they
            catalyze the formation of phosphatidylcholine.
  - term:
      id: GO:0003841
      label: 1-acylglycerol-3-phosphate O-acyltransferase activity
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1482547
    review:
      summary: Reactome annotation for AGPAT activity is consistent with
        experimental evidence demonstrating LPCAT2's ability to acylate LPA at
        sn-1.
      action: ACCEPT
      reason: AGPAT activity is experimentally verified for LPCAT2.
      additional_reference_ids:
        - PMID:20363836
      supported_by:
        - reference_id: PMID:20363836
          supporting_text: 'Enzymatic activity of the human 1-acylglycerol-3-phosphate-O-acyltransferase
            isoform 11: upregulated in breast and cervical cancers.'
  - term:
      id: GO:0047144
      label: 2-acylglycerol-3-phosphate O-acyltransferase activity
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1482533
    review:
      summary: This annotation suggests LPCAT2 can acylate
        2-acyl-sn-glycero-3-phosphate (sn-1 acylation). While LPCAT2 primarily
        acylates at sn-2 position, this represents a less well-characterized
        activity.
      action: KEEP_AS_NON_CORE
      reason: LPCAT2 primarily functions as an sn-2 acyltransferase. This
        activity is less well-characterized than the primary AGPAT activity at
        sn-2. Retaining as Reactome has curated this pathway.
  - term:
      id: GO:0005789
      label: endoplasmic reticulum membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1482533
    review:
      summary: ER membrane localization is consistent with experimental
        evidence.
      action: ACCEPT
      reason: ER membrane is the primary location, well-supported by IDA
        evidence.
  - term:
      id: GO:0005789
      label: endoplasmic reticulum membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1482547
    review:
      summary: Duplicate ER membrane annotation from different Reactome
        reaction.
      action: ACCEPT
      reason: ER membrane localization is well-established.
  - term:
      id: GO:0005783
      label: endoplasmic reticulum
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: ISS annotation based on mouse ortholog Q8BYI6. ER localization is
        confirmed by direct human experimental data.
      action: ACCEPT
      reason: ER localization is confirmed by IDA in human cells.
  - term:
      id: GO:0005795
      label: Golgi stack
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: Golgi localization inferred from mouse ortholog. UniProt mentions
        Golgi apparatus membrane by similarity. Less well-established than ER
        localization.
      action: KEEP_AS_NON_CORE
      reason: Golgi localization is supported by similarity evidence but not as
        strongly established as ER/lipid droplet localization by direct human
        experimental data.
  - term:
      id: GO:0006663
      label: platelet activating factor biosynthetic process
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: PAF biosynthesis is a core function of LPCAT2, which has lyso-PAF
        acetyltransferase activity (EC 2.3.1.67). The enzyme catalyzes
        conversion of lyso-PAF to PAF using acetyl-CoA, especially in
        inflammatory cells.
      action: ACCEPT
      reason: PAF biosynthesis is a verified core function of LPCAT2. The enzyme
        is distinguished from LPCAT1 by its inducible lyso-PAF acetyltransferase
        activity in inflammatory cells, analogous to COX-2.
  - term:
      id: GO:0047184
      label: 1-acylglycerophosphocholine O-acyltransferase activity
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: LPCAT activity inferred from mouse ortholog is confirmed by
        direct human experimental data (EC 2.3.1.23).
      action: ACCEPT
      reason: This is the primary molecular function of LPCAT2, confirmed by
        IDA.
  - term:
      id: GO:0047192
      label: 1-alkylglycerophosphocholine O-acetyltransferase activity
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: Lyso-PAF acetyltransferase activity (EC 2.3.1.67) is a core
        function of LPCAT2, enabling PAF biosynthesis. This inducible activity
        distinguishes LPCAT2 from LPCAT1.
      action: ACCEPT
      reason: Lyso-PAF acetyltransferase activity is a verified core function of
        LPCAT2, directly linked to its role in inflammatory PAF biosynthesis.
  - term:
      id: GO:0061024
      label: membrane organization
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: LPCAT2's role in PC synthesis contributes to membrane
        organization and lipid droplet biogenesis. The enzyme regulates lipid
        droplet number and size.
      action: KEEP_AS_NON_CORE
      reason: Membrane organization is a downstream consequence of LPCAT2's
        lipid remodeling activity rather than its primary function. Keep as
        non-core.
      supported_by:
        - reference_id: PMID:21498505
          supporting_text: LDs have the ability to locally synthesize PC and
            that this activity correlates with the LPCAT1 and -2 expression
            level.
  - term:
      id: GO:0000139
      label: Golgi membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: Golgi membrane localization is annotated based on UniProt
        subcellular location. UniProt notes Golgi apparatus membrane by
        similarity to mouse.
      action: KEEP_AS_NON_CORE
      reason: Golgi localization is less well-established than ER/lipid droplet
        localization. Keep as a secondary location annotation.
  - term:
      id: GO:0003841
      label: 1-acylglycerol-3-phosphate O-acyltransferase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: AGPAT activity is correctly annotated based on EC number
        2.3.1.51.
      action: ACCEPT
      reason: AGPAT activity is experimentally verified.
  - term:
      id: GO:0005509
      label: calcium ion binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: LPCAT2 contains EF-hand domains (IPR002048) that bind calcium.
        The enzyme's activity is Ca2+-dependent, distinguishing it from LPCAT1.
      action: ACCEPT
      reason: Calcium binding via EF-hand domains is structurally predicted and
        functionally relevant - LPCAT2's activity is Ca2+-dependent.
  - term:
      id: GO:0005789
      label: endoplasmic reticulum membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: ER membrane localization from UniProt subcellular location is
        consistent with experimental evidence.
      action: ACCEPT
      reason: ER membrane is the primary location, confirmed by IDA.
  - term:
      id: GO:0005811
      label: lipid droplet
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: Lipid droplet localization from UniProt is confirmed by
        experimental data.
      action: ACCEPT
      reason: Lipid droplet localization is experimentally verified in
        PMID:21498505.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: Plasma membrane localization is annotated by similarity to mouse
        ortholog in UniProt, but is not strongly supported by direct human
        experimental evidence.
      action: KEEP_AS_NON_CORE
      reason: Plasma membrane localization is noted by similarity in UniProt but
        is not as well-established as ER/lipid droplet localization.
  - term:
      id: GO:0006629
      label: lipid metabolic process
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: LPCAT2 is indeed involved in lipid metabolism, but this is a very
        general term.
      action: MARK_AS_OVER_ANNOTATED
      reason: This is too general. More specific terms like "phosphatidylcholine
        acyl-chain remodeling" (GO:0036151) and "platelet activating factor
        biosynthetic process" (GO:0006663) better describe LPCAT2's functions.
  - term:
      id: GO:0006650
      label: glycerophospholipid metabolic process
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: LPCAT2 is involved in glycerophospholipid metabolism,
        specifically PC and PAF biosynthesis. This is more specific than lipid
        metabolic process but still broad.
      action: KEEP_AS_NON_CORE
      reason: While accurate, more specific terms better describe LPCAT2's role.
        Keep as a broader context annotation.
  - term:
      id: GO:0008374
      label: O-acyltransferase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: O-acyltransferase activity is correct but generic. LPCAT2 has
        specific LPCAT and AGPAT activities.
      action: MARK_AS_OVER_ANNOTATED
      reason: This is a parent term of the more specific acyltransferase
        activities that LPCAT2 possesses. The specific activities are more
        informative.
  - term:
      id: GO:0008654
      label: phospholipid biosynthetic process
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: LPCAT2 contributes to phospholipid biosynthesis through PC
        remodeling and PA synthesis, but this is a broad term.
      action: KEEP_AS_NON_CORE
      reason: Accurate but broad. More specific terms like PC acyl-chain
        remodeling better describe the function.
  - term:
      id: GO:0016740
      label: transferase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: Transferase activity is far too general for LPCAT2.
      action: MARK_AS_OVER_ANNOTATED
      reason: This is a very high-level MF term that provides minimal
        information. The specific acyltransferase activities are much more
        informative.
  - term:
      id: GO:0016746
      label: acyltransferase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: Acyltransferase activity is correct but still quite general.
      action: MARK_AS_OVER_ANNOTATED
      reason: LPCAT2 has specific acyltransferase activities (LPCAT, AGPAT,
        lyso-PAF acetyltransferase) that are more informative than this parent
        term.
  - term:
      id: GO:0031984
      label: organelle subcompartment
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: This is an extremely generic cellular component term.
      action: MARK_AS_OVER_ANNOTATED
      reason: Too generic. LPCAT2 has specific localizations (ER membrane, lipid
        droplet) that are much more informative.
  - term:
      id: GO:0042171
      label: lysophosphatidic acid acyltransferase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: LPAAT/AGPAT activity is a verified function of LPCAT2 based on EC
        2.3.1.51.
      action: ACCEPT
      reason: This activity is experimentally demonstrated in PMID:20363836.
  - term:
      id: GO:0046872
      label: metal ion binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: LPCAT2 binds calcium via EF-hand domains.
      action: MODIFY
      reason: While correct, "calcium ion binding" (GO:0005509) is more specific
        and already annotated. This generic term should be replaced with the
        specific calcium binding.
      proposed_replacement_terms:
        - id: GO:0005509
          label: calcium ion binding
  - term:
      id: GO:0047159
      label: plasmalogen synthase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: Plasmalogen synthase activity (EC 2.3.1.25) for LPCAT2 is based
        on similarity to mouse ortholog Q8BYI6 in UniProt. This is a less
        well-characterized activity.
      action: KEEP_AS_NON_CORE
      reason: This activity is annotated by similarity in UniProt but lacks
        direct human experimental evidence. Keep as non-core pending
        verification.
  - term:
      id: GO:0047184
      label: 1-acylglycerophosphocholine O-acyltransferase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: LPCAT activity (EC 2.3.1.23) is a primary function experimentally
        verified.
      action: ACCEPT
      reason: Core enzymatic function confirmed by IDA evidence.
  - term:
      id: GO:0047192
      label: 1-alkylglycerophosphocholine O-acetyltransferase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: Lyso-PAF acetyltransferase activity (EC 2.3.1.67) is a core
        function for PAF biosynthesis.
      action: ACCEPT
      reason: This inducible acetyltransferase activity is central to LPCAT2's
        role in inflammation and PAF biosynthesis.
  - term:
      id: GO:0005783
      label: endoplasmic reticulum
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: ER localization is consistent with experimental evidence.
      action: ACCEPT
      reason: ER is the primary location, confirmed by IDA.
  - term:
      id: GO:0005795
      label: Golgi stack
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: Golgi localization from Ensembl Compara ortholog transfer.
      action: KEEP_AS_NON_CORE
      reason: Secondary localization, less well-established than ER/lipid
        droplet.
  - term:
      id: GO:0006663
      label: platelet activating factor biosynthetic process
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: PAF biosynthesis is a core function of LPCAT2 through its
        lyso-PAF acetyltransferase activity.
      action: ACCEPT
      reason: This is a defining function of LPCAT2, distinguishing it from
        LPCAT1.
  - term:
      id: GO:0016020
      label: membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: Generic membrane localization.
      action: MARK_AS_OVER_ANNOTATED
      reason: Too generic. LPCAT2 has specific membrane localizations (ER
        membrane, lipid droplet, Golgi membrane) that are more informative.
  - term:
      id: GO:0061024
      label: membrane organization
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: LPCAT2 contributes to membrane organization through PC synthesis
        and lipid droplet regulation.
      action: KEEP_AS_NON_CORE
      reason: This is a downstream effect of LPCAT2's lipid remodeling activity
        rather than its primary function.
  - term:
      id: GO:0006644
      label: phospholipid metabolic process
    evidence_type: IEA
    original_reference_id: GO_REF:0000041
    review:
      summary: LPCAT2 is involved in phospholipid metabolism via the Lands cycle
        and PAF biosynthesis.
      action: KEEP_AS_NON_CORE
      reason: Accurate but broad. More specific BP terms are available.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:32296183
    review:
      summary: LPCAT2 was identified as interacting with several proteins (EBP,
        ERGIC3, HSD17B13, KCNJ6, MFSD14B, RETREG3, RHBDD1) in the HuRI human
        reference interactome study. These are high-throughput Y2H interactions.
      action: KEEP_AS_NON_CORE
      reason: The "protein binding" term is uninformative and should generally
        be avoided. However, the interactions detected in this high-throughput
        study may be relevant to LPCAT2's function in the ER/lipid droplet. Keep
        as non-core pending more specific characterization of these
        interactions.
      supported_by:
        - reference_id: PMID:32296183
          supporting_text: Apr 8. A reference map of the human binary protein
            interactome.
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:0000043
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword
      mapping
    findings: []
  - id: GO_REF:0000044
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular
      Location vocabulary mapping
    findings: []
  - id: GO_REF:0000052
    title: Gene Ontology annotation based on curation of immunofluorescence data
    findings: []
  - id: GO_REF:0000107
    title: Automatic transfer of experimentally verified manual GO annotation
      data to orthologs using Ensembl Compara
    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: PMID:17182612
    title: "A single enzyme catalyzes both platelet-activating factor production and membrane biogenesis of inflammatory cells. Cloning and characterization of acetyl-CoA:LYSO-PAF acetyltransferase."
    findings:
      - statement: LPCAT2 was cloned and characterized as an acetyl-CoA:lyso-PAF
          acetyltransferase
        supporting_text: A single enzyme catalyzes both platelet-activating
          factor production and membrane biogenesis of inflammatory cells.
          Cloning and characterization of acetyl-CoA:lyso-PAF acetyltransferase.
      - statement: The enzyme catalyzes both PAF production and membrane PC
          synthesis
        supporting_text: Upon acute inflammatory stimulation with
          lipopolysaccharide, the activated enzyme utilizes acetyl-CoA more
          efficiently and produces PAF.
      - statement: LPCAT2 is inducible in inflammatory cells
        supporting_text: The enzyme was induced by bacterial endotoxin
          (lipopolysaccharide), which was suppressed by dexamethasone treatment.
  - id: PMID:20363836
    title: 'Enzymatic activity of the human 1-acylglycerol-3-phosphate-O-acyltransferase
      isoform 11: upregulated in breast and cervical cancers'
    findings:
      - statement: LPCAT2/AGPAT11 has AGPAT activity (LPA to PA conversion)
        supporting_text: In vitro enzymatic activity using lysates of Human
          Embryonic Kidney-293 cells infected with recombinant
          AGPAT11/LPCAT2/lyso platelet-activating factor-acetyltransferase cDNA
          adenovirus show that the protein has an AGPAT activity but lacks
          glycerol-3-phosphate acyltransferase enzymatic activity.
      - statement: Lacks GPAT activity
        supporting_text: the protein has an AGPAT activity but lacks
          glycerol-3-phosphate acyltransferase enzymatic activity.
      - statement: Localizes to ER in CHO and HeLa cells
        supporting_text: When AGPAT11/LPCAT2/lyso platelet-activating factor
          acetyltransferase cDNA was expressed in CHO and HeLa cells, the
          protein product localized to the endoplasmic reticulum.
      - statement: Upregulated in breast, cervical, and colorectal cancers
        supporting_text: Expression of AGPAT11 mRNA was significantly
          upregulated in human breast, cervical, and colorectal cancer tissues,
          indicating its adjuvant role in the progression of these cancers.
  - id: PMID:21498505
    title: Human lysophosphatidylcholine acyltransferases 1 and 2 are located in
      lipid droplets where they catalyze the formation of phosphatidylcholine
    findings:
      - statement: LPCAT2 localizes to both ER and lipid droplets
        supporting_text: Here, we show in various mammalian cell lines that both
          enzymes additionally localize to lipid droplets (LDs), which consist
          of a core of neutral lipids surrounded by a monolayer of phospholipid,
          mainly PC.
      - statement: LPCAT2 has dual ER and lipid droplet localization enabled by
          monotopic topology
        supporting_text: This dual localization is enabled by the monotopic
          topology of these enzymes demonstrated in this study.
      - statement: Catalyzes local PC synthesis on lipid droplets
        supporting_text: Furthermore, we show that LDs have the ability to
          locally synthesize PC and that this activity correlates with the
          LPCAT1 and -2 expression level.
  - id: PMID:32296183
    title: A reference map of the human binary protein interactome
    findings:
      - statement: High-throughput Y2H study identifying protein-protein
          interactions
  - id: Reactome:R-HSA-1482533
    title: 2-acyl LPC is acylated to PC by LPCAT
    findings: []
  - id: Reactome:R-HSA-1482547
    title: 1-acyl LPC is acylated to PC by LPCAT
    findings: []
  - id: Reactome:R-HSA-1482788
    title: Acyl chain remodelling of PC
    findings: []
  - id: file:human/LPCAT2/LPCAT2-deep-research-falcon.md
    title: Deep research on LPCAT2 function
    findings: []
core_functions:
  - molecular_function:
      id: GO:0047192
      label: 1-alkylglycerophosphocholine O-acetyltransferase activity
    description: Inducible lyso-PAF acetyltransferase activity (EC 2.3.1.67)
      converting lyso-PAF to platelet-activating factor (PAF) using acetyl-CoA.
      This Ca2+-dependent, LPS-inducible activity distinguishes LPCAT2 from
      constitutive LPCAT1 (analogous to COX-2 vs COX-1). Upon inflammatory
      stimulation via TLR4/p38 MAPK pathway, the enzyme preferentially uses
      acetyl-CoA for PAF biosynthesis.
    supported_by:
      - reference_id: PMID:17182612
        supporting_text: The enzyme was induced by bacterial endotoxin
          (lipopolysaccharide), which was suppressed by dexamethasone
          treatment... Upon acute inflammatory stimulation with
          lipopolysaccharide, the activated enzyme utilizes acetyl-CoA more
          efficiently and produces PAF.
    directly_involved_in:
      - id: GO:0006663
        label: platelet activating factor biosynthetic process
    locations:
      - id: GO:0005789
        label: endoplasmic reticulum membrane
  - molecular_function:
      id: GO:0047184
      label: 1-acylglycerophosphocholine O-acyltransferase activity
    description: Lysophosphatidylcholine acyltransferase activity (EC 2.3.1.23)
      converting lysoPC to PC by incorporating acyl-CoA (including
      arachidonoyl-CoA) at the sn-2 position. This reacylation step of the Lands
      cycle maintains membrane phospholipid composition. Under resting
      conditions, LPCAT2 preferentially catalyzes this acyltransferase reaction
      over the acetyltransferase reaction, contributing to membrane biogenesis.
      LPCAT2 also functions on lipid droplets where it catalyzes local PC
      synthesis.
    supported_by:
      - reference_id: PMID:21498505
        supporting_text: Human lysophosphatidylcholine acyltransferases 1 and 2
          are located in lipid droplets where they catalyze the formation of
          phosphatidylcholine
      - reference_id: PMID:17182612
        supporting_text: Under resting conditions, the enzyme prefers
          arachidonoyl-CoA and contributes to membrane biogenesis.
    directly_involved_in:
      - id: GO:0036151
        label: phosphatidylcholine acyl-chain remodeling
    locations:
      - id: GO:0005789
        label: endoplasmic reticulum membrane
      - id: GO:0005811
        label: lipid droplet
  - molecular_function:
      id: GO:0003841
      label: 1-acylglycerol-3-phosphate O-acyltransferase activity
    description: AGPAT activity (EC 2.3.1.51) converting lysophosphatidic acid
      (LPA) to phosphatidic acid (PA) by acylation at the sn-2 position.
      Demonstrated using C18:1 LPA as acyl acceptor. This activity contributes
      to de novo phospholipid biosynthesis distinct from the Lands cycle
      remodeling pathway.
    supported_by:
      - reference_id: PMID:20363836
        supporting_text: In vitro enzymatic activity using lysates of Human
          Embryonic Kidney-293 cells infected with recombinant
          AGPAT11/LPCAT2/lyso platelet-activating factor-acetyltransferase cDNA
          adenovirus show that the protein has an AGPAT activity but lacks
          glycerol-3-phosphate acyltransferase enzymatic activity.
    locations:
      - id: GO:0005789
        label: endoplasmic reticulum membrane
proposed_new_terms: []
suggested_questions:
  - question: What is the precise structural basis for LPCAT2's Ca2+-dependent
      activity and how do the EF-hand domains regulate enzyme function?
  - question: What is the relative contribution of LPCAT2 to PC synthesis in
      lipid droplets versus the ER, and how is this partitioning regulated?
  - question: How does LPCAT2 contribute to chemoresistance in colorectal
      cancer, and is this a viable therapeutic target?
suggested_experiments:
  - description: Structural studies (cryo-EM or X-ray crystallography) of LPCAT2
      with and without calcium to understand EF-hand domain regulation. Would
      elucidate the mechanism of Ca2+-dependent activation.
  - description: Lipidomics analysis comparing PC species in cells with LPCAT2
      knockdown versus LPCAT1 knockdown to define substrate preferences in vivo.
      Would clarify the distinct contributions of LPCAT1 and LPCAT2 to membrane
      PC composition.

Gene Description

Existing Annotations Review

Core Functions

AGPAT activity (EC 2.3.1.51) converting lysophosphatidic acid (LPA) to phosphatidic acid (PA) by acylation at the sn-2 position. Demonstrated using C18:1 LPA as acyl acceptor. This activity contributes to de novo phospholipid biosynthesis distinct from the Lands cycle remodeling pathway.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

Citations

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