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.

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

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