LPCAT1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0047184 1-acylglycerophosphocholine O-acyltransferase activity	IDA PMID:18156367 Mammalian acyl-CoA:lysophosphatidylcholine acyltransferase e...	ACCEPT	Summary: This is the primary and defining molecular function of LPCAT1. PMID:18156367 directly characterized LPCAT1 (Aytl2) as a lysophosphatidylcholine acyltransferase that converts lysoPC to PC using acyl-CoA donors. The study demonstrated activity with palmitoyl-CoA and lysoPC substrates. Reason: Core enzymatic function established by direct biochemical characterization. The enzyme catalyzes the conversion of 1-acyl-sn-glycero-3-phosphocholine + acyl-CoA to 1,2-diacyl-sn-glycero-3-phosphocholine + CoA. This is the canonical LPCAT reaction and represents the primary molecular function of the gene product. Supporting Evidence: PMID:18156367 The three murine Aytl proteins generated phosphatidylcholine from long-chain acyl-CoA and lysoPC when expressed in Escherichia coli membranes. PMID:18156367 Characterization of the product of the Aytl2 gene as the phosphatidylcholine reacylating enzyme in RBCs represents the identification of a plasma membrane lysophospholipid acyltransferase and establishes the function of a LPCAT protein. file:human/LPCAT1/LPCAT1-deep-research-falcon.md See deep research file for comprehensive analysis
GO:0047184 1-acylglycerophosphocholine O-acyltransferase activity	IDA PMID:21498505 Human lysophosphatidylcholine acyltransferases 1 and 2 are l...	ACCEPT	Summary: Additional IDA evidence confirming LPCAT activity. PMID:21498505 demonstrated that LPCAT1 and LPCAT2 catalyze PC formation at lipid droplets and in the ER. Reason: Independent confirmation of the core enzymatic activity. This study established the dual localization (ER and lipid droplets) and confirmed PC synthesis activity. Supporting Evidence: PMID:21498505 Here, we show in various mammalian cell lines that both enzymes additionally localize to lipid droplets (LDs)...Furthermore, we show that LDs have the ability to locally synthesize PC and that this activity correlates with the LPCAT1 and -2 expression level.
GO:0047184 1-acylglycerophosphocholine O-acyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation based on combined automated methods. Consistent with the IDA evidence from PMID:18156367 and PMID:21498505. Reason: The IEA annotation is consistent with experimental evidence. While redundant with IDA annotations, it provides additional computational support for the primary function.
GO:0047184 1-acylglycerophosphocholine O-acyltransferase activity	ISS GO_REF:0000024	ACCEPT	Summary: ISS annotation transferred from mouse ortholog Q3TFD2. Consistent with direct experimental evidence in human. Reason: Redundant with IDA evidence but correctly assigned. The mouse ortholog has been extensively characterized and the function is conserved.
GO:0042171 lysophosphatidic acid acyltransferase activity	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for LPAAT activity. UniProt indicates LPCAT1 can catalyze the conversion of lysophosphatidic acid (LPA) to phosphatidic acid (PA) by incorporating an acyl moiety at the sn-2 position (EC 2.3.1.51), based on similarity to rat Q1HAQ0. Reason: The phylogenetic inference is consistent with the enzyme's known substrate promiscuity. LPCAT1 belongs to the AGPAT/LPLAT family and can act on multiple lysophospholipid substrates. The IBA annotation represents a validated secondary function. Supporting Evidence: UniProtKB:Q8NF37 Catalyzes the conversion 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone (By similarity).
GO:0042171 lysophosphatidic acid acyltransferase activity	IEA GO_REF:0000117	ACCEPT	Summary: IEA annotation from ARBA machine learning. Consistent with the IBA annotation and UniProt functional assignment. Reason: Redundant with IBA annotation but consistent. The LPAAT activity is a recognized secondary function of LPCAT1.
GO:0003841 1-acylglycerol-3-phosphate O-acyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation for AGPAT activity (EC 2.3.1.51). This is essentially the same activity as GO:0042171 (lysophosphatidic acid acyltransferase activity). UniProt lists this activity based on similarity to rat Q1HAQ0. Reason: Valid secondary function. This term describes the same enzymatic activity as GO:0042171 but focuses on the substrate (1-acylglycerol-3-phosphate = LPA). The evidence from ISS and TAS annotations supports this function.
GO:0003841 1-acylglycerol-3-phosphate O-acyltransferase activity	TAS Reactome:R-HSA-1482539	ACCEPT	Summary: TAS annotation from Reactome for LPGAT activity (1-acyl LPG to PG). This represents LPCAT1's activity on lysophosphatidylglycerol. Reason: Reactome pathway annotation for lipid remodeling. LPCAT1 participates in PG acyl-chain remodeling in addition to its primary PC remodeling function.
GO:0003841 1-acylglycerol-3-phosphate O-acyltransferase activity	TAS Reactome:R-HSA-1482547	ACCEPT	Summary: TAS annotation from Reactome pathway for 1-acyl LPC acylation to PC. Reason: Valid Reactome pathway annotation. The Reactome pathway correctly represents LPCAT1's role in phospholipid acyl-chain remodeling.
GO:0003841 1-acylglycerol-3-phosphate O-acyltransferase activity	TAS Reactome:R-HSA-75885	ACCEPT	Summary: TAS annotation for PA synthesis (1-acyl LPA to PA). Part of the Reactome phospholipid biosynthesis pathway. Reason: Valid pathway annotation for LPCAT1's role in PA biosynthesis.
GO:0003841 1-acylglycerol-3-phosphate O-acyltransferase activity	ISS GO_REF:0000024	ACCEPT	Summary: ISS annotation transferred from rat ortholog Q1HAQ0. Reason: Consistent with other evidence for this activity. The rat ortholog has been characterized and the function is conserved.
GO:0047144 2-acylglycerol-3-phosphate O-acyltransferase activity	TAS Reactome:R-HSA-1482533	ACCEPT	Summary: TAS annotation for 2-acyl LPC acylation to PC. This represents activity on 2-acyl-substituted lysophospholipids, which are less common than 1-acyl species. Reason: The Reactome annotation indicates LPCAT1 can also act on 2-acyl lysophospholipids. This is a valid enzymatic activity for lysophospholipid acyltransferases.
GO:0047144 2-acylglycerol-3-phosphate O-acyltransferase activity	TAS Reactome:R-HSA-1482635	ACCEPT	Summary: TAS annotation for 2-acyl LPG acylation to PG. Reason: Consistent with LPCAT1's activity on various lysophospholipid substrates.
GO:0047192 1-alkylglycerophosphocholine O-acetyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation for lyso-PAF acetyltransferase activity (EC 2.3.1.67). UniProt lists LPCAT1 as having this activity based on similarity to mouse Q3TFD2. This relates to platelet-activating factor (PAF) biosynthesis. Reason: LPCAT1 is also known as Lyso-PAF acetyltransferase (LysoPAFAT). This activity converts lyso-PAF to PAF by acetylation at the sn-2 position. The alternate name reflects this established secondary function. Supporting Evidence: UniProtKB:Q8NF37 AltName: Full=Acetyl-CoA:lyso-platelet-activating factor acetyltransferase; Short=Lyso-PAF acetyltransferase; Short=LysoPAFAT
GO:0047192 1-alkylglycerophosphocholine O-acetyltransferase activity	ISS GO_REF:0000024	ACCEPT	Summary: ISS annotation for lyso-PAF acetyltransferase activity transferred from mouse Q3TFD2. Reason: Consistent with IEA annotation. The activity is well-documented in the mouse ortholog and expected to be conserved in human LPCAT1.
GO:0047191 1-alkylglycerophosphocholine O-acyltransferase activity	IEA GO_REF:0000107	ACCEPT	Summary: IEA annotation from Ensembl Compara for activity on ether-linked lysophospholipids. This represents acylation (not acetylation) of alkyl-linked lysoPC. Reason: This activity is related to but distinct from GO:0047192. LPCAT1 can acylate ether-linked lysophospholipids, contributing to plasmalogen biosynthesis.
GO:0047159 plasmalogen synthase activity	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation for plasmalogen synthase activity (EC 2.3.1.25). This is the 1-alkenylglycerophosphocholine O-acyltransferase activity. Reason: LPCAT1 can acylate vinyl-ether (alkenyl) linked lysophospholipids, contributing to plasmalogen biosynthesis. UniProt lists EC 2.3.1.25 based on mouse ortholog similarity. Supporting Evidence: UniProtKB:Q8NF37 AltName: Full=1-alkenylglycerophosphocholine O-acyltransferase; EC=2.3.1.25 {ECO:0000250\|UniProtKB:Q3TFD2}
GO:0047159 plasmalogen synthase activity	ISS GO_REF:0000024	ACCEPT	Summary: ISS annotation for plasmalogen synthase activity transferred from mouse Q3TFD2. Reason: Consistent with IEA annotation. Represents a valid secondary enzymatic activity.
GO:0016746 acyltransferase activity	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	Summary: Generic acyltransferase activity term. While correct, more specific terms are available and annotated (GO:0047184, GO:0003841, etc.). Reason: This is a parent term of the more specific acyltransferase activities. The specific child terms (1-acylglycerophosphocholine O-acyltransferase, AGPAT, etc.) are already annotated and provide more informative annotations.
GO:0008374 O-acyltransferase activity	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: Generic O-acyltransferase activity from InterPro domain annotation. While technically correct, more specific terms are available. Reason: This is a parent term of the specific O-acyltransferase activities annotated. The child terms provide much more informative functional annotation.
GO:0016740 transferase activity	IEA GO_REF:0000043	MARK AS OVER ANNOTATED	Summary: Very generic transferase activity term from UniProt keyword mapping. Reason: This is an extremely broad parent term. The specific acyltransferase activities annotated provide the informative functional description. This term adds no additional information.
GO:0005509 calcium ion binding	IEA GO_REF:0000002	ACCEPT	Summary: Calcium ion binding annotation from InterPro EF-hand domain recognition. LPCAT1 contains two EF-hand domains (residues 379-414 and 451-486) that have predicted calcium binding residues. PMID:18156367 notes that calcium and magnesium modulate LPCAT activity. Reason: The EF-hand domains are structurally validated and calcium modulation of activity has been demonstrated. However, it's notable that UniProt states the acyltransferase activity itself is calcium-independent (by similarity), suggesting the EF-hands may have a regulatory rather than catalytic role. Supporting Evidence: PMID:18156367 Calcium and magnesium modulated LPCAT activity of both Aytl1 and -2 proteins that exhibit EF-hand motifs at the C terminus. UniProtKB:Q8NF37 DOMAIN 379..414 EF-hand 1; DOMAIN 451..486 EF-hand 2
GO:0046872 metal ion binding	IEA GO_REF:0000043	MARK AS OVER ANNOTATED	Summary: Generic metal ion binding term from UniProt keyword mapping. Reason: This is a parent term of GO:0005509 (calcium ion binding). Since the more specific calcium binding term is already annotated, this adds no additional information.
GO:0005783 endoplasmic reticulum	IDA PMID:21498505 Human lysophosphatidylcholine acyltransferases 1 and 2 are l...	ACCEPT	Summary: Direct experimental evidence for ER localization. PMID:21498505 demonstrated ER localization using immunofluorescence and established the monotopic topology of LPCAT1 in ER membranes. Reason: Core subcellular localization established by direct experimental evidence. The ER is the primary site of LPCAT1 function in phospholipid remodeling. The di-lysine motif (KKLD at C-terminus) confers ER retention. 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 UniProtKB:Q8NF37 MOTIF 531..534 Di-lysine motif; The di-lysine motif may confer endoplasmic reticulum localization.
GO:0005783 endoplasmic reticulum	IDA GO_REF:0000052	ACCEPT	Summary: IDA annotation from HPA immunofluorescence curation. Consistent with PMID:21498505. Reason: Independent confirmation of ER localization from Human Protein Atlas data.
GO:0005783 endoplasmic reticulum	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic inference for ER localization, consistent with IDA evidence. Reason: ER localization is conserved across orthologs and supported by experimental evidence.
GO:0005783 endoplasmic reticulum	IEA GO_REF:0000107	ACCEPT	Summary: IEA annotation from Ensembl Compara, consistent with IDA evidence. Reason: Redundant with IDA annotations but correctly assigned.
GO:0005783 endoplasmic reticulum	ISS GO_REF:0000024	ACCEPT	Summary: ISS annotation transferred from mouse ortholog Q3TFD2. Reason: Consistent with direct experimental evidence for human LPCAT1.
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: IEA annotation from UniProt subcellular location vocabulary. UniProt indicates LPCAT1 is an ER membrane protein with single-pass type II topology. Reason: More specific than GO:0005783 and accurately describes the membrane localization. PMID:21498505 demonstrated the membrane topology. Supporting Evidence: UniProtKB:Q8NF37 SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass type II membrane protein
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-1482533	ACCEPT	Summary: TAS annotation from Reactome pathway for PC synthesis. Reason: Consistent with IEA and IDA evidence for ER membrane localization.
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-1482539	ACCEPT	Summary: TAS annotation from Reactome pathway. Reason: Consistent with other evidence for ER membrane localization.
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-1482547	ACCEPT	Summary: TAS annotation from Reactome pathway. Reason: Consistent with other evidence for ER membrane localization.
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-1482635	ACCEPT	Summary: TAS annotation from Reactome pathway. Reason: Consistent with other evidence for ER membrane localization.
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-75885	ACCEPT	Summary: TAS annotation from Reactome pathway. Reason: Consistent with other evidence for ER membrane localization.
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-8873834	ACCEPT	Summary: TAS annotation from Reactome for STARD10 transport of PC from ER membrane. Reason: Consistent with LPCAT1's role in PC synthesis at the ER membrane.
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-8873923	ACCEPT	Summary: TAS annotation from Reactome for STARD10-LPCAT1-PC complex. Reason: Supports the ER membrane localization of LPCAT1.
GO:0005811 lipid droplet	IDA PMID:21498505 Human lysophosphatidylcholine acyltransferases 1 and 2 are l...	ACCEPT	Summary: Direct experimental evidence for lipid droplet localization. PMID:21498505 is the key study demonstrating that LPCAT1 and LPCAT2 localize to lipid droplets in addition to ER, enabled by their monotopic membrane topology. Reason: Core secondary localization established by direct experimental evidence. The study showed that lipid droplets can locally synthesize PC and this activity correlates with LPCAT1/2 expression. Supporting Evidence: PMID:21498505 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. PMID:21498505 This dual localization is enabled by the monotopic topology of these enzymes demonstrated in this study.
GO:0005811 lipid droplet	IDA GO_REF:0000052	ACCEPT	Summary: IDA annotation from HPA immunofluorescence curation, consistent with PMID:21498505. Reason: Independent confirmation of lipid droplet localization from HPA data.
GO:0005811 lipid droplet	IEA GO_REF:0000044	ACCEPT	Summary: IEA annotation from UniProt subcellular location vocabulary. Reason: Consistent with IDA evidence. UniProt documents lipid droplet localization.
GO:0000139 Golgi membrane	IEA GO_REF:0000044	ACCEPT	Summary: IEA annotation for Golgi membrane localization from UniProt subcellular location vocabulary. UniProt indicates Golgi localization based on similarity to mouse ortholog. Reason: Golgi localization is a secondary site. The protein is primarily ER-resident but can also be found in Golgi, consistent with its role in membrane lipid remodeling along the secretory pathway. Supporting Evidence: UniProtKB:Q8NF37 SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000250\|UniProtKB:Q3TFD2}
GO:0005794 Golgi apparatus	IEA GO_REF:0000107	ACCEPT	Summary: IEA annotation from Ensembl Compara for Golgi apparatus. Reason: Consistent with UniProt annotation. GO:0000139 (Golgi membrane) is more specific, but this parent term is also valid.
GO:0005794 Golgi apparatus	ISS GO_REF:0000024	ACCEPT	Summary: ISS annotation for Golgi apparatus transferred from mouse ortholog Q3TFD2. Reason: Consistent with IEA annotations. The mouse ortholog has been shown to localize to the Golgi.
GO:0005886 plasma membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: IEA annotation for plasma membrane localization. PMID:18156367 identified LPCAT1 (Aytl2) as the PC reacylating enzyme in erythrocytes, suggesting plasma membrane localization in this cell type. Reason: Plasma membrane localization appears to be cell-type specific (e.g., erythrocytes). The primary localizations are ER and lipid droplets. Plasma membrane localization may represent a specialized function in RBCs. Supporting Evidence: PMID:18156367 Characterization of the product of the Aytl2 gene as the phosphatidylcholine reacylating enzyme in RBCs represents the identification of a plasma membrane lysophospholipid acyltransferase
GO:0005886 plasma membrane	TAS Reactome:R-HSA-6798739	KEEP AS NON CORE	Summary: TAS annotation from Reactome for exocytosis of azurophil granule membrane proteins. This represents LPCAT1 presence at the plasma membrane during neutrophil degranulation. Reason: This is a specialized context (neutrophil degranulation) where LPCAT1 may reach the plasma membrane through vesicular trafficking. Not a primary localization.
GO:0035577 azurophil granule membrane	TAS Reactome:R-HSA-6798739	KEEP AS NON CORE	Summary: TAS annotation from Reactome indicating LPCAT1 presence in azurophil granule membrane during neutrophil degranulation. Reason: This is a highly specialized localization specific to neutrophils. The annotation is from Reactome's neutrophil degranulation pathway and represents a cell-type specific context rather than a core localization.
GO:0016020 membrane	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Very generic membrane term from Ensembl Compara. Reason: This is an extremely broad parent term. More specific membrane localizations (ER membrane, Golgi membrane, lipid droplet) are already annotated and provide much more informative descriptions. Keeping as non-core for consistency with HDA evidence.
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	KEEP AS NON CORE	Summary: HDA annotation from a high-throughput membrane proteomics study of NK cells. LPCAT1 was identified as a membrane protein in this proteomics screen. Reason: While the HDA evidence is valid (LPCAT1 is a membrane protein), the term is overly generic. More specific membrane localizations are annotated. However, the experimental basis (proteomics) provides independent confirmation of membrane association. Supporting Evidence: PMID:19946888 Mass spectrometric analysis identified 1843 proteins with high confidence scores...approximately 40% of the identified proteins were predicted as plausible membrane proteins.
GO:0036151 phosphatidylcholine acyl-chain remodeling	IDA PMID:21498505 Human lysophosphatidylcholine acyltransferases 1 and 2 are l...	ACCEPT	Summary: Direct experimental evidence for PC acyl-chain remodeling. This is the core biological process representing LPCAT1's function in the Lands cycle. Reason: This is the primary biological process of LPCAT1. The enzyme operates in the Lands cycle to remodel PC acyl chains, controlling membrane phospholipid composition. PMID:21498505 demonstrated PC synthesis activity. Supporting Evidence: PMID:21498505 Phosphatidylcholine (PC) is synthesized by two different pathways, the Lands cycle and the Kennedy pathway. The recently identified key enzymes of the Lands cycle, lysophosphatidylcholine acyltransferase 1 and 2 (LPCAT1 and -2)... PMID:21498505 we show that LDs have the ability to locally synthesize PC and that this activity correlates with the LPCAT1 and -2 expression level
GO:0036151 phosphatidylcholine acyl-chain remodeling	TAS Reactome:R-HSA-1482788	ACCEPT	Summary: TAS annotation from Reactome for PC acyl-chain remodeling pathway. Reason: Consistent with IDA evidence. The Reactome pathway correctly captures LPCAT1's role in PC remodeling.
GO:0036148 phosphatidylglycerol acyl-chain remodeling	TAS Reactome:R-HSA-1482925	ACCEPT	Summary: TAS annotation for PG acyl-chain remodeling from Reactome. LPCAT1 can act on lysophosphatidylglycerol as an alternative substrate. Reason: Secondary biological process reflecting LPCAT1's activity on lysoPG substrates. This is less prominent than PC remodeling but represents a valid pathway role.
GO:0006654 phosphatidic acid biosynthetic process	TAS Reactome:R-HSA-1483166	ACCEPT	Summary: TAS annotation for PA biosynthesis from Reactome. LPCAT1 can convert LPA to PA. Reason: Represents LPCAT1's secondary role in PA biosynthesis through its LPAAT/AGPAT activity. This is part of the broader phospholipid biosynthetic network.
GO:0008654 phospholipid biosynthetic process	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: IEA annotation for phospholipid biosynthesis. This is a broader parent term of the more specific PC remodeling process. Reason: While technically correct, GO:0036151 (PC acyl-chain remodeling) is more specific and better describes LPCAT1's primary function. This parent term provides less informative annotation.
GO:0008654 phospholipid biosynthetic process	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ISS annotation for phospholipid biosynthesis transferred from mouse ortholog. Reason: Parent term of more specific processes. Less informative than child terms.
GO:0006644 phospholipid metabolic process	IEA GO_REF:0000041	MARK AS OVER ANNOTATED	Summary: IEA annotation from UniPathway mapping for phospholipid metabolism. Reason: This is a very broad parent term. More specific biological processes (PC remodeling, PA biosynthesis) are already annotated and provide more informative descriptions.
GO:0006629 lipid metabolic process	IEA GO_REF:0000043	MARK AS OVER ANNOTATED	Summary: Very generic lipid metabolism term from UniProt keyword mapping. Reason: This is an extremely broad parent term. The specific phospholipid remodeling processes are already annotated and provide much more informative descriptions of LPCAT1's biological function.

Gene Description

Existing Annotations Review

Core Functions

Catalyzes the acylation of lysophosphatidic acid (LPA) to phosphatidic acid (PA) at the sn-2 position, contributing to de novo phospholipid biosynthesis.

Catalyzes the acylation of lysophosphatidylglycerol (lysoPG) to phosphatidylglycerol (PG), contributing to PG acyl-chain remodeling. This activity is relevant for surfactant phospholipid composition.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

📄 View Raw YAML