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.

Core Functions

Catalyzes the acylation of lysophosphatidylcholine (lysoPC) to phosphatidylcholine (PC) in the Lands cycle, with preference for saturated fatty acyl-CoA donors (especially palmitoyl-CoA). Critical for generating dipalmitoylphosphatidylcholine (DPPC) for pulmonary surfactant and for controlling membrane phospholipid saturation.

Molecular Function:

1-acylglycerophosphocholine O-acyltransferase activity

Directly Involved In:

phosphatidylcholine acyl-chain remodeling

Cellular Locations:

endoplasmic reticulum membrane lipid droplet

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

Molecular Function:

1-acylglycerol-3-phosphate O-acyltransferase activity

Directly Involved In:

phosphatidic acid biosynthetic process

Cellular Locations:

endoplasmic reticulum membrane

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

Molecular Function:

1-acylglycerol-3-phosphate O-acyltransferase activity

Directly Involved In:

phosphatidylglycerol acyl-chain remodeling

Cellular Locations:

endoplasmic reticulum membrane

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

EF-hand domain (IPR002048) mapped to calcium ion binding
LPCAT1-like domain (IPR045252) mapped to O-acyltransferase activity

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

Annotations transferred from well-characterized mouse (Q3TFD2) and rat (Q1HAQ0) orthologs

GO_REF:0000033

Annotation inferences using phylogenetic trees

Phylogenetic analysis supports ER localization and LPAAT activity across LPCAT1 orthologs

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

Subcellular locations mapped from UniProt annotations

GO_REF:0000052

Gene Ontology annotation based on curation of immunofluorescence data

Human Protein Atlas data supports ER and lipid droplet localization

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:18156367

Mammalian acyl-CoA:lysophosphatidylcholine acyltransferase enzymes.

LPCAT1 (Aytl2) characterized as PC-reacylating enzyme in erythrocytes

"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."
Generated PC from long-chain acyl-CoA and lysoPC substrates

"The three murine Aytl proteins generated phosphatidylcholine from long-chain acyl-CoA and lysoPC when expressed in Escherichia coli membranes."
Calcium and magnesium modulate LPCAT activity

"Calcium and magnesium modulated LPCAT activity of both Aytl1 and -2 proteins that exhibit EF-hand motifs at the C terminus."
Contains EF-hand motifs at C-terminus

"Calcium and magnesium modulated LPCAT activity of both Aytl1 and -2 proteins that exhibit EF-hand motifs at the C terminus."

PMID:19946888

Defining the membrane proteome of NK cells.

LPCAT1 identified in membrane proteome of NK-like cells

"Mass spectrometric analysis identified 1843 proteins with high confidence scores...approximately 40% of the identified proteins were predicted as plausible membrane proteins."

PMID:21498505

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

LPCAT1 and LPCAT2 localize 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."
Dual localization enabled by monotopic membrane topology

"This dual localization is enabled by the monotopic topology of these enzymes demonstrated in this study."
Lipid droplets can locally synthesize PC

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

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

Reactome:R-HSA-1482533

2-acyl LPC is acylated to PC by LPCAT

Reactome:R-HSA-1482539

1-acyl LPG is acylated to PG by LPGAT

Reactome:R-HSA-1482547

1-acyl LPC is acylated to PC by LPCAT

Reactome:R-HSA-1482635

2-acyl LPG is acylated to PG by LPGAT

Reactome:R-HSA-1482788

Acyl chain remodelling of PC

Reactome:R-HSA-1482925

Acyl chain remodelling of PG

Reactome:R-HSA-1483166

Synthesis of PA

Reactome:R-HSA-6798739

Exocytosis of azurophil granule membrane proteins

LPCAT1 present at plasma membrane and azurophil granule membrane during neutrophil degranulation

Reactome:R-HSA-75885

1-acyl LPA is acylated to PA by AGPAT (LPAAT)

Reactome:R-HSA-8873834

STARD10 transports PC from ER membrane to lamellar body membrane

Reactome:R-HSA-8873923

STARD10 binds LPCAT1 and PC

file:human/LPCAT1/LPCAT1-deep-research-falcon.md

Deep research on LPCAT1 function

Suggested Experiments

Experiment: Substrate specificity profiling comparing ER-localized vs lipid droplet-localized LPCAT1

Experiment: Structural studies to understand the basis for acyl-CoA selectivity

Experiment: In vivo assessment of LPCAT1 contribution to pulmonary surfactant DPPC in human alveolar cells

Deep Research

Falcon

(LPCAT1-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 13 citations 2025-12-21T22:40:08.707389

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.

Comprehensive Research Report: Human LPCAT1 (UniProt Q8NF37)

Identity verification and scope
- Target gene/protein: LPCAT1 (lysophosphatidylcholine acyltransferase 1), UniProt Q8NF37, Homo sapiens. LPCAT1 is a lysophospholipid acyltransferase (LPLAT) that operates in the Lands cycle to remodel membrane phospholipids. It is placed within AGPAT/LPLAT families and is recognized across recent peer‑reviewed literature as a human ER-resident enzyme linked to lipid remodeling and ferroptosis resistance (review/commentary 2024). The domain/family context aligns with acyltransferase/LPLAT annotations provided (AGPAT/LPLAT8 aliases) (May 2024, Cancers; Aug 13, 2024, Cell Death & Differentiation) (korbecki2024phospholipidacyltransferasescharacterization pages 6-8, korbecki2024phospholipidacyltransferasescharacterization pages 16-17, lee2024rewiringcancercell pages 1-2).

1) Key concepts and definitions
- Enzyme class and pathway: LPCAT1 is a lysophosphatidylcholine acyltransferase in the Lands cycle that re‑esterifies lysophospholipids using acyl‑CoA donors, thereby controlling phosphatidylcholine (PC) acyl chain composition and membrane biophysical properties (Aug 13, 2024; commentary summarizing recent work). In human cells it is ER‑localized, also reported at lipid droplets and in the nucleus in certain contexts (May 2024) (lee2024rewiringcancercell pages 1-2, korbecki2024phospholipidacyltransferasescharacterization pages 8-9, korbecki2024phospholipidacyltransferasescharacterization pages 6-8).
- Molecular function: LPCAT1 catalyzes acylation of lysoPC to PC and participates in PC biosynthesis/remodeling. It has been implicated in forming dipalmitoyl‑PC (DPPC), the key surface tension–reducing phospholipid of pulmonary surfactant (May 2024) (korbecki2024phospholipidacyltransferasescharacterization pages 8-9, korbecki2024phospholipidacyltransferasescharacterization pages 6-8).
- Cellular localization: Predominantly endoplasmic reticulum; also detected at lipid droplets and with a nuclear role reported in histone H4 palmitoylation (May 2024) (korbecki2024phospholipidacyltransferasescharacterization pages 26-27, korbecki2024phospholipidacyltransferasescharacterization pages 6-8).

2) Catalytic reaction and substrate specificity
- Reaction: Acyl‑CoA + lysoPC → CoA + PC. This is the canonical LPLAT reaction within the Lands cycle (2024 commentary/review) (lee2024rewiringcancercell pages 1-2, korbecki2024phospholipidacyltransferasescharacterization pages 6-8).
- Acyl donor preference: Reviews report LPCAT1 activity with multiple acyl‑CoA donors; 2024 commentary synthesizing recent data indicates LPCAT1 preferentially channels saturated fatty acyl‑CoA (SFA‑CoA) into lysophospholipids in cancer models, increasing SFA‑containing phospholipids and membrane saturation that opposes ferroptosis (Aug 13, 2024) (lee2024rewiringcancercell pages 1-2). A 2024 review table lists oleoyl‑CoA as a preferred donor in some assays, reflecting assay/model variability across studies (May 2024) (korbecki2024phospholipidacyltransferasescharacterization pages 16-17, korbecki2024phospholipidacyltransferasescharacterization pages 8-9).
- Substrate scope: Primary substrate is lysoPC; activity toward other lysophospholipids (e.g., lysoPG) is noted in review summaries. LPCAT family enzymes also intersect with platelet‑activating factor (PAF) metabolism in some cellular contexts, though primary LPCAT1 function is PC remodeling (May 2024) (korbecki2024phospholipidacyltransferasescharacterization pages 6-8, korbecki2024phospholipidacyltransferasescharacterization pages 27-29).

3) Subcellular localization and site of action
- ER localization is consistently reported and aligns with a role in membrane phospholipid remodeling (May 2024) (korbecki2024phospholipidacyltransferasescharacterization pages 6-8).
- Lipid droplets: LPCAT1 has been localized to lipid droplets where it catalyzes PC formation on droplet surfaces (May 2024) (korbecki2024phospholipidacyltransferasescharacterization pages 26-27).
- Nuclear context: Evidence indicates a noncanonical role where LPCAT1 contributes to histone H4 O‑palmitoylation linked to transcriptional regulation; this is reported in review summaries (May 2024) (korbecki2024phospholipidacyltransferasescharacterization pages 26-27, korbecki2024phospholipidacyltransferasescharacterization pages 16-17).

4) Physiological roles and pathways
- Pulmonary surfactant and DPPC maturation: Reviews place LPCAT1 as responsible for DPPC production and thus surfactant lipid maturation in lung, consistent with its high pulmonary expression (May 2024) (korbecki2024phospholipidacyltransferasescharacterization pages 8-9). While AT2/lamellar body specifics are not detailed in the cited excerpts, the functional link to DPPC is explicit in these sources (May 2024) (korbecki2024phospholipidacyltransferasescharacterization pages 8-9).
- Ferroptosis regulation: LPCAT1 remodels membrane lipids toward higher SFA content, reducing PUFA content and sensitivity to peroxidation. Genetic or pharmacologic suppression of LPCAT1 increases ferroptosis susceptibility; conversely, overexpression promotes ferroptosis resistance and tumor growth. LPCAT1 protective effects can be independent of canonical GPX4/FSP1/GCH1/DHODH defenses (Aug 13, 2024) (lee2024rewiringcancercell pages 1-2).
- Lands cycle and KRAS biology: Ferroptosis can be induced in KRAS‑mutant lung cancer by targeting de novo lipogenesis and the Lands cycle, emphasizing the reliance on lipid remodeling to cope with oxidative stress, placing LPCAT enzymes centrally in this vulnerability (Jul 21, 2022) (lee2024rewiringcancercell pages 1-2).

5) Recent developments and latest research (2023–2024 emphasis)
- 2024 expert commentary: Upregulation of LPCAT1 in ferroptosis‑resistant cancer cells; LPCAT1 drives incorporation of SFA‑CoA into phospholipids, elevates saturation, and confers ferroptosis resistance. Inhibition of LPCAT1 synergizes with ferroptosis inducers to suppress tumor growth in preclinical models (Aug 13, 2024; includes mechanistic integration and therapeutic angle) (lee2024rewiringcancercell pages 1-2).
- 2024 review synthesis: Consolidates human LPCAT1’s ER localization, involvement in DPPC formation, high lung expression, lipid droplet/nuclear roles, and associations with reduced PUFA content and ferroptosis resistance; also compiles disease links and drug resistance associations (May 2024) (korbecki2024phospholipidacyltransferasescharacterization pages 8-9, korbecki2024phospholipidacyltransferasescharacterization pages 26-27, korbecki2024phospholipidacyltransferasescharacterization pages 6-8, korbecki2024phospholipidacyltransferasescharacterization pages 16-17, korbecki2024phospholipidacyltransferasescharacterization pages 27-29).
- 2023 ferroptosis‑sensitization landscape: Pharmacologic remodeling of lipid metabolism (e.g., PLA2G7/Lp‑PLA2 inhibition) enhances ferroptosis and underscores the central role of lipid enzymes such as LPCAT/LPLATs in determining ferroptosis thresholds, providing a framework in which LPCAT1 acts as a resistance node (Sep 26, 2023) (lee2024rewiringcancercell pages 1-2).

6) Disease links, current applications, and real‑world implementations
- Cancer overexpression and prognosis: Elevated LPCAT1 expression is linked with poorer prognosis and aggressive features across several tumors (e.g., lung adenocarcinoma, hepatocellular carcinoma, prostate cancer) in integrative reviews compiling multi‑study evidence. Mechanistically, LPCAT1 contributes to proliferation, EMT, metastasis, and therapeutic resistance (May 2024) (korbecki2024phospholipidacyltransferasescharacterization pages 27-29, korbecki2024phospholipidacyltransferasescharacterization pages 16-17, korbecki2024phospholipidacyltransferasescharacterization pages 8-9).
- Therapeutic targeting and combinations: Preclinical evidence supports inhibiting LPCAT1 to sensitize tumors to ferroptosis inducers, representing a strategy to overcome lipid peroxidation resistance. This is positioned as complementary to (and in some contexts independent of) GPX4/FSP1 defense pathways (Aug 13, 2024) (lee2024rewiringcancercell pages 1-2).
- Lung biology and surfactant: Given LPCAT1’s role in DPPC production and predominant lung expression, it is a key enzyme in surfactant lipid maturation; this has implications for pulmonary disorders where surfactant homeostasis is perturbed (May 2024) (korbecki2024phospholipidacyltransferasescharacterization pages 8-9).

7) Expert opinions and analysis
- 2024 commentary perspective (Cell Death & Differentiation): Highlights LPCAT1 as a central lipid‑metabolism enzyme rewiring cancer cell death through membrane saturation control, and advocates LPCAT1 inhibition to unmask ferroptosis vulnerabilities, especially when canonical antioxidant systems are circumvented (Aug 13, 2024) (lee2024rewiringcancercell pages 1-2).
- 2024 integrative review (Cancers): Presents LPCAT1 as a multi‑compartment lipid enzyme with roles in Lands cycle remodeling, transcriptional control via histone palmitoylation, ferroptosis resistance, and broad oncologic associations; proposes LPCAT1 as a therapeutic target and biomarker in cancer (May 2024) (korbecki2024phospholipidacyltransferasescharacterization pages 8-9, korbecki2024phospholipidacyltransferasescharacterization pages 26-27, korbecki2024phospholipidacyltransferasescharacterization pages 16-17, korbecki2024phospholipidacyltransferasescharacterization pages 27-29, korbecki2024phospholipidacyltransferasescharacterization pages 6-8).

8) Relevant statistics and data
- While the excerpts compiled here do not include numerical hazard ratios or effect sizes, the 2024 commentary reports that LPCAT1 overexpression promotes tumor growth and that LPCAT1 inhibition synergizes with ferroptosis inducers to suppress tumor growth in vivo, indicating measurable preclinical efficacy in combined strategies (Aug 13, 2024). The 2024 review aggregates multiple studies linking higher LPCAT1 expression with worse survival across cancers and with resistance to chemotherapeutics (May 2024) (lee2024rewiringcancercell pages 1-2, korbecki2024phospholipidacyltransferasescharacterization pages 27-29, korbecki2024phospholipidacyltransferasescharacterization pages 16-17).

Notes on surfactant cell biology
- The sources cited explicitly tie LPCAT1 to DPPC formation and high lung expression, supporting a role in surfactant lipid maturation. However, the excerpts available here do not provide primary experimental details on alveolar type II cell specificity, lamellar body localization, or direct ABCA3 pathway integration; further primary literature would be required for those specific mechanistic localizations (May 2024) (korbecki2024phospholipidacyltransferasescharacterization pages 8-9).

Conclusion
Human LPCAT1 (Q8NF37) is an ER‑localized lysophospholipid acyltransferase in the Lands cycle that acylates lysoPC using acyl‑CoA donors to remodel PC species. It contributes to DPPC production in lung and remodels membranes toward higher saturation, counteracting ferroptosis by limiting PUFA‑peroxidation substrates. Elevated LPCAT1 associates with poor prognosis and therapy resistance across cancers, and preclinical work indicates that inhibiting LPCAT1 synergizes with ferroptosis inducers to suppress tumor growth. These roles position LPCAT1 as a mechanistically anchored biomarker and therapeutic target at the intersection of lipid remodeling, surfactant biology, and ferroptosis regulation (Aug 13, 2024; May 2024; Sep 26, 2023; Jul 21, 2022) (lee2024rewiringcancercell pages 1-2, korbecki2024phospholipidacyltransferasescharacterization pages 8-9, korbecki2024phospholipidacyltransferasescharacterization pages 26-27, korbecki2024phospholipidacyltransferasescharacterization pages 16-17, korbecki2024phospholipidacyltransferasescharacterization pages 27-29, korbecki2024phospholipidacyltransferasescharacterization pages 6-8).

Cited sources with URLs and publication dates
- Lee H, Zhuang L, Gan B. Rewiring cancer cell death: LPCAT1 shapes lipid composition and ferroptosis resistance. Cell Death & Differentiation. Published online Aug 13, 2024. URL: https://doi.org/10.1038/s41418-024-01364-9 (lee2024rewiringcancercell pages 1-2)
- Korbecki J, et al. Phospholipid Acyltransferases: Characterization and Involvement of the Enzymes in Metabolic and Cancer Diseases. Cancers. Published May 2024;16:2115. URL: https://doi.org/10.3390/cancers16112115 (korbecki2024phospholipidacyltransferasescharacterization pages 8-9, korbecki2024phospholipidacyltransferasescharacterization pages 26-27, korbecki2024phospholipidacyltransferasescharacterization pages 16-17, korbecki2024phospholipidacyltransferasescharacterization pages 27-29, korbecki2024phospholipidacyltransferasescharacterization pages 6-8)
- Oh M, et al. The lipoprotein-associated phospholipase A2 inhibitor Darapladib sensitises cancer cells to ferroptosis by remodelling lipid metabolism. Nature Communications. Published Sep 26, 2023. URL: https://doi.org/10.1038/s41467-023-41462-9 (contextual ferroptosis landscape) (lee2024rewiringcancercell pages 1-2)
- Bartolacci C, et al. Targeting de novo lipogenesis and the Lands cycle induces ferroptosis in KRAS-mutant lung cancer. Nature Communications. Published Jul 21, 2022. URL: https://doi.org/10.1038/s41467-022-31963-4 (lee2024rewiringcancercell pages 1-2)
- Yang X, et al. Ferroptosis as a new tool for tumor suppression through lipid peroxidation. Communications Biology. Published Nov 2024. URL: https://doi.org/10.1038/s42003-024-07180-8 (overview of ferroptosis regulators and lipid metabolism) (lee2024rewiringcancercell pages 1-2)

References

(korbecki2024phospholipidacyltransferasescharacterization pages 6-8): 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.
(korbecki2024phospholipidacyltransferasescharacterization pages 16-17): 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.
(lee2024rewiringcancercell pages 1-2): Hyemin Lee, Li Zhuang, and Boyi Gan. Rewiring cancer cell death: lpcat1 shapes lipid composition and ferroptosis resistance. Cell death and differentiation, 31:1101-1103, Aug 2024. URL: https://doi.org/10.1038/s41418-024-01364-9, doi:10.1038/s41418-024-01364-9. This article has 2 citations and is from a domain leading 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.
(korbecki2024phospholipidacyltransferasescharacterization pages 26-27): 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.
(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.

Citations

lee2024rewiringcancercell pages 1-2
korbecki2024phospholipidacyltransferasescharacterization pages 6-8
korbecki2024phospholipidacyltransferasescharacterization pages 26-27
korbecki2024phospholipidacyltransferasescharacterization pages 8-9
korbecki2024phospholipidacyltransferasescharacterization pages 16-17
korbecki2024phospholipidacyltransferasescharacterization pages 27-29
https://doi.org/10.1038/s41418-024-01364-9
https://doi.org/10.3390/cancers16112115
https://doi.org/10.1038/s41467-023-41462-9
https://doi.org/10.1038/s41467-022-31963-4
https://doi.org/10.1038/s42003-024-07180-8
https://doi.org/10.3390/cancers16112115,
https://doi.org/10.1038/s41418-024-01364-9,

📄 View Raw YAML

---
id: Q8NF37
gene_symbol: LPCAT1
aliases: [AYTL2, PFAAP3, LysoPAFAT, LPCAT-1]
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is an ER-resident
  enzyme that operates in the Lands cycle to remodel membrane phospholipids. It catalyzes
  the acylation of lysophosphatidylcholine (lysoPC) to phosphatidylcholine (PC) using
  acyl-CoA donors, with preference for saturated fatty acyl-CoAs. The enzyme is critical
  for dipalmitoylphosphatidylcholine (DPPC) production in pulmonary surfactant. LPCAT1
  also localizes to lipid droplets where it contributes to local PC synthesis. Additionally,
  it has reported activity toward lysophosphatidic acid (LPA) and lysophosphatidylglycerol
  (LPG). The enzyme contains EF-hand domains and a catalytic HXXXXD motif. Recent
  research has linked LPCAT1 to ferroptosis resistance in cancer through membrane
  lipid saturation.
existing_annotations:
  - term:
      id: GO:0047184
      label: 1-acylglycerophosphocholine O-acyltransferase activity
    evidence_type: IDA
    original_reference_id: PMID:18156367
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:18156367
          supporting_text: The three murine Aytl proteins generated phosphatidylcholine
            from long-chain acyl-CoA and lysoPC when expressed in Escherichia coli
            membranes.
        - reference_id: PMID:18156367
          supporting_text: 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.
        - reference_id: file:human/LPCAT1/LPCAT1-deep-research-falcon.md
          supporting_text: See deep research file for comprehensive analysis
  - term:
      id: GO:0047184
      label: 1-acylglycerophosphocholine O-acyltransferase activity
    evidence_type: IDA
    original_reference_id: PMID:21498505
    review:
      summary: Additional IDA evidence confirming LPCAT activity. PMID:21498505 demonstrated
        that LPCAT1 and LPCAT2 catalyze PC formation at lipid droplets and in the
        ER.
      action: ACCEPT
      reason: Independent confirmation of the core enzymatic activity. This study
        established the dual localization (ER and lipid droplets) and confirmed PC
        synthesis activity.
      supported_by:
        - reference_id: PMID:21498505
          supporting_text: 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.
  - term:
      id: GO:0047184
      label: 1-acylglycerophosphocholine O-acyltransferase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: IEA annotation based on combined automated methods. Consistent with
        the IDA evidence from PMID:18156367 and PMID:21498505.
      action: ACCEPT
      reason: The IEA annotation is consistent with experimental evidence. While redundant
        with IDA annotations, it provides additional computational support for the
        primary function.
  - term:
      id: GO:0047184
      label: 1-acylglycerophosphocholine O-acyltransferase activity
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: ISS annotation transferred from mouse ortholog Q3TFD2. Consistent with
        direct experimental evidence in human.
      action: ACCEPT
      reason: Redundant with IDA evidence but correctly assigned. The mouse ortholog
        has been extensively characterized and the function is conserved.
  - term:
      id: GO:0042171
      label: lysophosphatidic acid acyltransferase activity
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: UniProtKB:Q8NF37
          supporting_text: 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).
  - term:
      id: GO:0042171
      label: lysophosphatidic acid acyltransferase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: IEA annotation from ARBA machine learning. Consistent with the IBA
        annotation and UniProt functional assignment.
      action: ACCEPT
      reason: Redundant with IBA annotation but consistent. The LPAAT activity is
        a recognized secondary function of LPCAT1.
  - term:
      id: GO:0003841
      label: 1-acylglycerol-3-phosphate O-acyltransferase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      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.
      action: ACCEPT
      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.
  - term:
      id: GO:0003841
      label: 1-acylglycerol-3-phosphate O-acyltransferase activity
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1482539
    review:
      summary: TAS annotation from Reactome for LPGAT activity (1-acyl LPG to PG).
        This represents LPCAT1's activity on lysophosphatidylglycerol.
      action: ACCEPT
      reason: Reactome pathway annotation for lipid remodeling. LPCAT1 participates
        in PG acyl-chain remodeling in addition to its primary PC remodeling function.
  - term:
      id: GO:0003841
      label: 1-acylglycerol-3-phosphate O-acyltransferase activity
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1482547
    review:
      summary: TAS annotation from Reactome pathway for 1-acyl LPC acylation to PC.
      action: ACCEPT
      reason: Valid Reactome pathway annotation. The Reactome pathway correctly represents
        LPCAT1's role in phospholipid acyl-chain remodeling.
  - term:
      id: GO:0003841
      label: 1-acylglycerol-3-phosphate O-acyltransferase activity
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-75885
    review:
      summary: TAS annotation for PA synthesis (1-acyl LPA to PA). Part of the Reactome
        phospholipid biosynthesis pathway.
      action: ACCEPT
      reason: Valid pathway annotation for LPCAT1's role in PA biosynthesis.
  - term:
      id: GO:0003841
      label: 1-acylglycerol-3-phosphate O-acyltransferase activity
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: ISS annotation transferred from rat ortholog Q1HAQ0.
      action: ACCEPT
      reason: Consistent with other evidence for this activity. The rat ortholog has
        been characterized and the function is conserved.
  - term:
      id: GO:0047144
      label: 2-acylglycerol-3-phosphate O-acyltransferase activity
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1482533
    review:
      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.
      action: ACCEPT
      reason: The Reactome annotation indicates LPCAT1 can also act on 2-acyl lysophospholipids.
        This is a valid enzymatic activity for lysophospholipid acyltransferases.
  - term:
      id: GO:0047144
      label: 2-acylglycerol-3-phosphate O-acyltransferase activity
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1482635
    review:
      summary: TAS annotation for 2-acyl LPG acylation to PG.
      action: ACCEPT
      reason: Consistent with LPCAT1's activity on various lysophospholipid substrates.
  - term:
      id: GO:0047192
      label: 1-alkylglycerophosphocholine O-acetyltransferase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: UniProtKB:Q8NF37
          supporting_text: 'AltName: Full=Acetyl-CoA:lyso-platelet-activating factor
            acetyltransferase; Short=Lyso-PAF acetyltransferase; Short=LysoPAFAT'
  - term:
      id: GO:0047192
      label: 1-alkylglycerophosphocholine O-acetyltransferase activity
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: ISS annotation for lyso-PAF acetyltransferase activity transferred
        from mouse Q3TFD2.
      action: ACCEPT
      reason: Consistent with IEA annotation. The activity is well-documented in the
        mouse ortholog and expected to be conserved in human LPCAT1.
  - term:
      id: GO:0047191
      label: 1-alkylglycerophosphocholine O-acyltransferase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation from Ensembl Compara for activity on ether-linked lysophospholipids.
        This represents acylation (not acetylation) of alkyl-linked lysoPC.
      action: ACCEPT
      reason: This activity is related to but distinct from GO:0047192. LPCAT1 can
        acylate ether-linked lysophospholipids, contributing to plasmalogen biosynthesis.
  - term:
      id: GO:0047159
      label: plasmalogen synthase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: IEA annotation for plasmalogen synthase activity (EC 2.3.1.25). This
        is the 1-alkenylglycerophosphocholine O-acyltransferase activity.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: UniProtKB:Q8NF37
          supporting_text: 'AltName: Full=1-alkenylglycerophosphocholine O-acyltransferase;
            EC=2.3.1.25 {ECO:0000250|UniProtKB:Q3TFD2}'
  - term:
      id: GO:0047159
      label: plasmalogen synthase activity
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: ISS annotation for plasmalogen synthase activity transferred from mouse
        Q3TFD2.
      action: ACCEPT
      reason: Consistent with IEA annotation. Represents a valid secondary enzymatic
        activity.
  - term:
      id: GO:0016746
      label: acyltransferase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: Generic acyltransferase activity term. While correct, more specific
        terms are available and annotated (GO:0047184, GO:0003841, etc.).
      action: MARK_AS_OVER_ANNOTATED
      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.
  - term:
      id: GO:0008374
      label: O-acyltransferase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: Generic O-acyltransferase activity from InterPro domain annotation.
        While technically correct, more specific terms are available.
      action: MARK_AS_OVER_ANNOTATED
      reason: This is a parent term of the specific O-acyltransferase activities annotated.
        The child terms provide much more informative functional annotation.
  - term:
      id: GO:0016740
      label: transferase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: Very generic transferase activity term from UniProt keyword mapping.
      action: MARK_AS_OVER_ANNOTATED
      reason: This is an extremely broad parent term. The specific acyltransferase
        activities annotated provide the informative functional description. This
        term adds no additional information.
  - term:
      id: GO:0005509
      label: calcium ion binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:18156367
          supporting_text: Calcium and magnesium modulated LPCAT activity of both
            Aytl1 and -2 proteins that exhibit EF-hand motifs at the C terminus.
        - reference_id: UniProtKB:Q8NF37
          supporting_text: DOMAIN 379..414 EF-hand 1; DOMAIN 451..486 EF-hand 2
  - term:
      id: GO:0046872
      label: metal ion binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: Generic metal ion binding term from UniProt keyword mapping.
      action: MARK_AS_OVER_ANNOTATED
      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.
  - term:
      id: GO:0005783
      label: endoplasmic reticulum
    evidence_type: IDA
    original_reference_id: PMID:21498505
    review:
      summary: Direct experimental evidence for ER localization. PMID:21498505 demonstrated
        ER localization using immunofluorescence and established the monotopic topology
        of LPCAT1 in ER membranes.
      action: ACCEPT
      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.
      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
        - reference_id: UniProtKB:Q8NF37
          supporting_text: MOTIF 531..534 Di-lysine motif; The di-lysine motif may
            confer endoplasmic reticulum localization.
  - term:
      id: GO:0005783
      label: endoplasmic reticulum
    evidence_type: IDA
    original_reference_id: GO_REF:0000052
    review:
      summary: IDA annotation from HPA immunofluorescence curation. Consistent with
        PMID:21498505.
      action: ACCEPT
      reason: Independent confirmation of ER localization from Human Protein Atlas
        data.
  - term:
      id: GO:0005783
      label: endoplasmic reticulum
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: Phylogenetic inference for ER localization, consistent with IDA evidence.
      action: ACCEPT
      reason: ER localization is conserved across orthologs and supported by experimental
        evidence.
  - term:
      id: GO:0005783
      label: endoplasmic reticulum
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation from Ensembl Compara, consistent with IDA evidence.
      action: ACCEPT
      reason: Redundant with IDA annotations but correctly assigned.
  - term:
      id: GO:0005783
      label: endoplasmic reticulum
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: ISS annotation transferred from mouse ortholog Q3TFD2.
      action: ACCEPT
      reason: Consistent with direct experimental evidence for human LPCAT1.
  - term:
      id: GO:0005789
      label: endoplasmic reticulum membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: IEA annotation from UniProt subcellular location vocabulary. UniProt
        indicates LPCAT1 is an ER membrane protein with single-pass type II topology.
      action: ACCEPT
      reason: More specific than GO:0005783 and accurately describes the membrane
        localization. PMID:21498505 demonstrated the membrane topology.
      supported_by:
        - reference_id: UniProtKB:Q8NF37
          supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane;
            Single-pass type II membrane protein'
  - term:
      id: GO:0005789
      label: endoplasmic reticulum membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1482533
    review:
      summary: TAS annotation from Reactome pathway for PC synthesis.
      action: ACCEPT
      reason: Consistent with IEA and IDA evidence for ER membrane localization.
  - term:
      id: GO:0005789
      label: endoplasmic reticulum membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1482539
    review:
      summary: TAS annotation from Reactome pathway.
      action: ACCEPT
      reason: Consistent with other evidence for ER membrane localization.
  - term:
      id: GO:0005789
      label: endoplasmic reticulum membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1482547
    review:
      summary: TAS annotation from Reactome pathway.
      action: ACCEPT
      reason: Consistent with other evidence for ER membrane localization.
  - term:
      id: GO:0005789
      label: endoplasmic reticulum membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1482635
    review:
      summary: TAS annotation from Reactome pathway.
      action: ACCEPT
      reason: Consistent with other evidence for ER membrane localization.
  - term:
      id: GO:0005789
      label: endoplasmic reticulum membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-75885
    review:
      summary: TAS annotation from Reactome pathway.
      action: ACCEPT
      reason: Consistent with other evidence for ER membrane localization.
  - term:
      id: GO:0005789
      label: endoplasmic reticulum membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8873834
    review:
      summary: TAS annotation from Reactome for STARD10 transport of PC from ER membrane.
      action: ACCEPT
      reason: Consistent with LPCAT1's role in PC synthesis at the ER membrane.
  - term:
      id: GO:0005789
      label: endoplasmic reticulum membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8873923
    review:
      summary: TAS annotation from Reactome for STARD10-LPCAT1-PC complex.
      action: ACCEPT
      reason: Supports the ER membrane localization of LPCAT1.
  - term:
      id: GO:0005811
      label: lipid droplet
    evidence_type: IDA
    original_reference_id: PMID:21498505
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:21498505
          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.
        - reference_id: PMID:21498505
          supporting_text: This dual localization is enabled by the monotopic topology
            of these enzymes demonstrated in this study.
  - term:
      id: GO:0005811
      label: lipid droplet
    evidence_type: IDA
    original_reference_id: GO_REF:0000052
    review:
      summary: IDA annotation from HPA immunofluorescence curation, consistent with
        PMID:21498505.
      action: ACCEPT
      reason: Independent confirmation of lipid droplet localization from HPA data.
  - term:
      id: GO:0005811
      label: lipid droplet
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: IEA annotation from UniProt subcellular location vocabulary.
      action: ACCEPT
      reason: Consistent with IDA evidence. UniProt documents lipid droplet localization.
  - term:
      id: GO:0000139
      label: Golgi membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: IEA annotation for Golgi membrane localization from UniProt subcellular
        location vocabulary. UniProt indicates Golgi localization based on similarity
        to mouse ortholog.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: UniProtKB:Q8NF37
          supporting_text: 'SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000250|UniProtKB:Q3TFD2}'
  - term:
      id: GO:0005794
      label: Golgi apparatus
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation from Ensembl Compara for Golgi apparatus.
      action: ACCEPT
      reason: Consistent with UniProt annotation. GO:0000139 (Golgi membrane) is more
        specific, but this parent term is also valid.
  - term:
      id: GO:0005794
      label: Golgi apparatus
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: ISS annotation for Golgi apparatus transferred from mouse ortholog
        Q3TFD2.
      action: ACCEPT
      reason: Consistent with IEA annotations. The mouse ortholog has been shown to
        localize to the Golgi.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      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.
      action: KEEP_AS_NON_CORE
      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.
      supported_by:
        - reference_id: PMID:18156367
          supporting_text: Characterization of the product of the Aytl2 gene as the
            phosphatidylcholine reacylating enzyme in RBCs represents the identification
            of a plasma membrane lysophospholipid acyltransferase
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6798739
    review:
      summary: TAS annotation from Reactome for exocytosis of azurophil granule membrane
        proteins. This represents LPCAT1 presence at the plasma membrane during neutrophil
        degranulation.
      action: KEEP_AS_NON_CORE
      reason: This is a specialized context (neutrophil degranulation) where LPCAT1
        may reach the plasma membrane through vesicular trafficking. Not a primary
        localization.
  - term:
      id: GO:0035577
      label: azurophil granule membrane
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6798739
    review:
      summary: TAS annotation from Reactome indicating LPCAT1 presence in azurophil
        granule membrane during neutrophil degranulation.
      action: KEEP_AS_NON_CORE
      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.
  - term:
      id: GO:0016020
      label: membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: Very generic membrane term from Ensembl Compara.
      action: KEEP_AS_NON_CORE
      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.
  - term:
      id: GO:0016020
      label: membrane
    evidence_type: HDA
    original_reference_id: PMID:19946888
    review:
      summary: HDA annotation from a high-throughput membrane proteomics study of
        NK cells. LPCAT1 was identified as a membrane protein in this proteomics screen.
      action: KEEP_AS_NON_CORE
      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.
      supported_by:
        - reference_id: PMID:19946888
          supporting_text: Mass spectrometric analysis identified 1843 proteins with
            high confidence scores...approximately 40% of the identified proteins
            were predicted as plausible membrane proteins.
  - term:
      id: GO:0036151
      label: phosphatidylcholine acyl-chain remodeling
    evidence_type: IDA
    original_reference_id: PMID:21498505
    review:
      summary: Direct experimental evidence for PC acyl-chain remodeling. This is
        the core biological process representing LPCAT1's function in the Lands cycle.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:21498505
          supporting_text: 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)...
        - reference_id: PMID:21498505
          supporting_text: we show that LDs have the ability to locally synthesize
            PC and that this activity correlates with the LPCAT1 and -2 expression
            level
  - term:
      id: GO:0036151
      label: phosphatidylcholine acyl-chain remodeling
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1482788
    review:
      summary: TAS annotation from Reactome for PC acyl-chain remodeling pathway.
      action: ACCEPT
      reason: Consistent with IDA evidence. The Reactome pathway correctly captures
        LPCAT1's role in PC remodeling.
  - term:
      id: GO:0036148
      label: phosphatidylglycerol acyl-chain remodeling
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1482925
    review:
      summary: TAS annotation for PG acyl-chain remodeling from Reactome. LPCAT1 can
        act on lysophosphatidylglycerol as an alternative substrate.
      action: ACCEPT
      reason: Secondary biological process reflecting LPCAT1's activity on lysoPG
        substrates. This is less prominent than PC remodeling but represents a valid
        pathway role.
  - term:
      id: GO:0006654
      label: phosphatidic acid biosynthetic process
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1483166
    review:
      summary: TAS annotation for PA biosynthesis from Reactome. LPCAT1 can convert
        LPA to PA.
      action: ACCEPT
      reason: Represents LPCAT1's secondary role in PA biosynthesis through its LPAAT/AGPAT
        activity. This is part of the broader phospholipid biosynthetic network.
  - term:
      id: GO:0008654
      label: phospholipid biosynthetic process
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: IEA annotation for phospholipid biosynthesis. This is a broader parent
        term of the more specific PC remodeling process.
      action: KEEP_AS_NON_CORE
      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.
  - term:
      id: GO:0008654
      label: phospholipid biosynthetic process
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: ISS annotation for phospholipid biosynthesis transferred from mouse
        ortholog.
      action: KEEP_AS_NON_CORE
      reason: Parent term of more specific processes. Less informative than child
        terms.
  - term:
      id: GO:0006644
      label: phospholipid metabolic process
    evidence_type: IEA
    original_reference_id: GO_REF:0000041
    review:
      summary: IEA annotation from UniPathway mapping for phospholipid metabolism.
      action: MARK_AS_OVER_ANNOTATED
      reason: This is a very broad parent term. More specific biological processes
        (PC remodeling, PA biosynthesis) are already annotated and provide more informative
        descriptions.
  - term:
      id: GO:0006629
      label: lipid metabolic process
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: Very generic lipid metabolism term from UniProt keyword mapping.
      action: MARK_AS_OVER_ANNOTATED
      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.
references:
  - id: GO_REF:0000002
    title: Gene Ontology annotation through association of InterPro records with GO
      terms
    findings:
      - statement: EF-hand domain (IPR002048) mapped to calcium ion binding
      - statement: LPCAT1-like domain (IPR045252) mapped to O-acyltransferase activity
  - id: GO_REF:0000024
    title: Manual transfer of experimentally-verified manual GO annotation data to
      orthologs by curator judgment of sequence similarity
    findings:
      - statement: Annotations transferred from well-characterized mouse (Q3TFD2)
          and rat (Q1HAQ0) orthologs
  - id: GO_REF:0000033
    title: Annotation inferences using phylogenetic trees
    findings:
      - statement: Phylogenetic analysis supports ER localization and LPAAT activity
          across LPCAT1 orthologs
  - 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:
      - statement: Subcellular locations mapped from UniProt annotations
  - id: GO_REF:0000052
    title: Gene Ontology annotation based on curation of immunofluorescence data
    findings:
      - statement: Human Protein Atlas data supports ER and lipid droplet localization
  - 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:18156367
    title: Mammalian acyl-CoA:lysophosphatidylcholine acyltransferase enzymes.
    findings:
      - statement: LPCAT1 (Aytl2) characterized as PC-reacylating enzyme in erythrocytes
        supporting_text: 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.
      - statement: Generated PC from long-chain acyl-CoA and lysoPC substrates
        supporting_text: The three murine Aytl proteins generated phosphatidylcholine
          from long-chain acyl-CoA and lysoPC when expressed in Escherichia coli membranes.
      - statement: Calcium and magnesium modulate LPCAT activity
        supporting_text: Calcium and magnesium modulated LPCAT activity of both Aytl1
          and -2 proteins that exhibit EF-hand motifs at the C terminus.
      - statement: Contains EF-hand motifs at C-terminus
        supporting_text: Calcium and magnesium modulated LPCAT activity of both Aytl1
          and -2 proteins that exhibit EF-hand motifs at the C terminus.
  - id: PMID:19946888
    title: Defining the membrane proteome of NK cells.
    findings:
      - statement: LPCAT1 identified in membrane proteome of NK-like cells
        supporting_text: Mass spectrometric analysis identified 1843 proteins with
          high confidence scores...approximately 40% of the identified proteins were
          predicted as plausible membrane proteins.
  - id: PMID:21498505
    title: Human lysophosphatidylcholine acyltransferases 1 and 2 are located in lipid
      droplets where they catalyze the formation of phosphatidylcholine.
    findings:
      - statement: LPCAT1 and LPCAT2 localize 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: Dual localization enabled by monotopic membrane topology
        supporting_text: This dual localization is enabled by the monotopic topology
          of these enzymes demonstrated in this study.
      - statement: Lipid droplets can locally synthesize PC
        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.
      - statement: PC synthesis activity correlates with LPCAT1/2 expression
        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: Reactome:R-HSA-1482533
    title: 2-acyl LPC is acylated to PC by LPCAT
    findings: []
  - id: Reactome:R-HSA-1482539
    title: 1-acyl LPG is acylated to PG by LPGAT
    findings: []
  - id: Reactome:R-HSA-1482547
    title: 1-acyl LPC is acylated to PC by LPCAT
    findings: []
  - id: Reactome:R-HSA-1482635
    title: 2-acyl LPG is acylated to PG by LPGAT
    findings: []
  - id: Reactome:R-HSA-1482788
    title: Acyl chain remodelling of PC
    findings: []
  - id: Reactome:R-HSA-1482925
    title: Acyl chain remodelling of PG
    findings: []
  - id: Reactome:R-HSA-1483166
    title: Synthesis of PA
    findings: []
  - id: Reactome:R-HSA-6798739
    title: Exocytosis of azurophil granule membrane proteins
    findings:
      - statement: LPCAT1 present at plasma membrane and azurophil granule membrane
          during neutrophil degranulation
  - id: Reactome:R-HSA-75885
    title: 1-acyl LPA is acylated to PA by AGPAT (LPAAT)
    findings: []
  - id: Reactome:R-HSA-8873834
    title: STARD10 transports PC from ER membrane to lamellar body membrane
    findings: []
  - id: Reactome:R-HSA-8873923
    title: STARD10 binds LPCAT1 and PC
    findings: []
  - id: file:human/LPCAT1/LPCAT1-deep-research-falcon.md
    title: Deep research on LPCAT1 function
    findings: []
core_functions:
  - description: Catalyzes the acylation of lysophosphatidylcholine (lysoPC) to phosphatidylcholine
      (PC) in the Lands cycle, with preference for saturated fatty acyl-CoA donors
      (especially palmitoyl-CoA). Critical for generating dipalmitoylphosphatidylcholine
      (DPPC) for pulmonary surfactant and for controlling membrane phospholipid saturation.
    molecular_function:
      id: GO:0047184
      label: 1-acylglycerophosphocholine O-acyltransferase activity
    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
    anatomical_locations:
      - id: UBERON:0002048
        label: lung
  - description: Catalyzes the acylation of lysophosphatidic acid (LPA) to phosphatidic
      acid (PA) at the sn-2 position, contributing to de novo phospholipid biosynthesis.
    molecular_function:
      id: GO:0003841
      label: 1-acylglycerol-3-phosphate O-acyltransferase activity
    directly_involved_in:
      - id: GO:0006654
        label: phosphatidic acid biosynthetic process
    locations:
      - id: GO:0005789
        label: endoplasmic reticulum membrane
  - description: Catalyzes the acylation of lysophosphatidylglycerol (lysoPG) to phosphatidylglycerol
      (PG), contributing to PG acyl-chain remodeling. This activity is relevant for
      surfactant phospholipid composition.
    molecular_function:
      id: GO:0003841
      label: 1-acylglycerol-3-phosphate O-acyltransferase activity
    directly_involved_in:
      - id: GO:0036148
        label: phosphatidylglycerol acyl-chain remodeling
    locations:
      - id: GO:0005789
        label: endoplasmic reticulum membrane
suggested_questions:
  - question: Does LPCAT1 have distinct substrate preferences when localized to lipid
      droplets versus ER?
  - question: What is the relative contribution of LPCAT1 vs LPCAT2 to total cellular
      PC synthesis?
  - question: Is the reported nuclear localization and histone H4 palmitoylation activity
      physiologically significant?
  - question: How does calcium binding to the EF-hand domains regulate LPCAT1 activity?
suggested_experiments:
  - description: Substrate specificity profiling comparing ER-localized vs lipid droplet-localized
      LPCAT1
  - description: Structural studies to understand the basis for acyl-CoA selectivity
  - description: In vivo assessment of LPCAT1 contribution to pulmonary surfactant
      DPPC in human alveolar cells

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

Citations

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