ALE1 (YOR175C; also LPT1/SLC4) encodes the major acyl-CoA-dependent lysophospholipid acyltransferase (LPLAT) of budding yeast, a multi-pass membrane-bound O-acyltransferase (MBOAT family, orthologous to human MBOAT1/2) residing in the endoplasmic reticulum and enriched in the mitochondria-associated ER membrane. Ale1 has broad acceptor specificity: it acylates lysophosphatidylcholine (its preferred substrate), lysophosphatidylethanolamine and lysophosphatidic acid, and to a lesser extent lysophosphatidylserine, -inositol and -glycerol, preferring unsaturated (monounsaturated) acyl-CoAs, and it also has lyso-PAF acetyltransferase activity. It is the main LPCAT and LPEAT of the cell, re-acylating imported or endogenously generated lysolipids (including LPC formed by Gpc1 in the PC deacylation/reacylation pathway) and thereby contributing to phospholipid synthesis and acyl-chain remodeling. Ale1 also acts as a secondary 1-acylglycerol-3-phosphate acyltransferase alongside Slc1: ale1 slc1 double mutants are inviable, showing that Ale1 can supply the phosphatidic acid needed for glycerolipid synthesis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003841 1-acylglycerol-3-phosphate O-acyltransferase activity | EXP PMID:17890783 LPT1 encodes a membrane-bound O-acyltransferase involved in ... | ACCEPT | Summary: Tamaki et al. 2007: purified/expressed Lpt1 (Ale1) acylates a wide range of lysophospholipids including lysophosphatidic acid, and the lpt1 slc1 double mutant is synthetically lethal, indicating Ale1 contributes PA synthesis. Correct; Ale1 is the secondary LPAAT after Slc1. Supporting Evidence: PMID:17890783 These results indicate that, in concert with Slc1, Lpt1 plays a central role in PA biosynthesis, which is essential for cell viability. |
| GO:0003841 1-acylglycerol-3-phosphate O-acyltransferase activity | EXP PMID:18154737 A family of eukaryotic lysophospholipid acyltransferases wit... | ACCEPT | Summary: Stahl et al. 2008 assayed ScLPLAT (Ale1) with LPA. They note that Ale1, unlike Slc1, cannot efficiently use LPA generated in situ from glycerol-3-phosphate in vitro, so LPAAT is a genuine but secondary activity of this broad-specificity enzyme. Accept the activity. Supporting Evidence: PMID:18154737 The budding yeast ALE1 gene encodes a lysophospholipid acyltransferase (LPLAT) with broad specificity. |
| GO:0003841 1-acylglycerol-3-phosphate O-acyltransferase activity | EXP PMID:26643989 Possible Role of Different Yeast and Plant Lysophospholipid:... | ACCEPT | Summary: Jasieniecka-Gazarkiewicz et al. 2016 assayed Ale1 expressed in ale1 microsomes against oleoyl-lysophospholipids; Ale1 had high activity with lysoPtdOH (LPA), lysoPtdCho and lysoPtdEtn. Supports LPAAT activity. Supporting Evidence: PMID:26643989 Ale1 also showed broad acyl specificity, having high activities towards lysoPtdCho, lysoPtdOH, and lysoPtdEtn with highest activity towards lysoPtdCho (Fig. 1d). |
| GO:0003841 1-acylglycerol-3-phosphate O-acyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT node PTN001016739 seeded by yeast ALE1 and Candida ALE1; the node sits on the fungal LPLAT (MBOAT) subfamily, and the experimental grounding includes Ale1 itself. Sound. |
| GO:0003841 1-acylglycerol-3-phosphate O-acyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: RHEA:19709/RHEA:37131 and EC 2.3.1.51 mapping from the UniProt catalytic-activity records. Correct for Ale1, which has experimentally shown LPAAT activity. |
| GO:0003841 1-acylglycerol-3-phosphate O-acyltransferase activity | IGI PMID:17675291 SLC1 and SLC4 encode partially redundant acyl-coenzyme A 1-a... | ACCEPT | Summary: Benghezal et al. 2007: SLC4 (= ALE1) down-regulation in slc1 cells strongly reduced microsomal LPAAT activity and the slc1 slc4 double deletion is lethal. Genetic interaction with SLC1 (SGD:S000002210) supports Ale1 as the second LPAAT. Supporting Evidence: PMID:17675291 SLC4 harbors a membrane-bound O-acyltransferase motif and down-regulation of SLC4 strongly reduces 1-acyl-sn-glycerol-3-phosphate acyltransferase activity in microsomes from slc1Delta cells. |
| GO:0003841 1-acylglycerol-3-phosphate O-acyltransferase activity | IMP PMID:17675291 SLC1 and SLC4 encode partially redundant acyl-coenzyme A 1-a... | ACCEPT | Summary: Same study, mutant evidence: loss of SLC4/ALE1 in slc1 background reduces LPAAT activity. Correct. Supporting Evidence: PMID:17675291 Here we show that SLC4 (Yor175c), a gene of hitherto unknown function, encodes a second 1-acyl-sn-glycerol-3-phosphate acyltransferase. |
| GO:0003841 1-acylglycerol-3-phosphate O-acyltransferase activity | IMP PMID:17726007 Identification of a novel lysophospholipid acyltransferase i... | ACCEPT | Summary: Jain et al. 2007: LPT1 deletion had little effect on LPAAT activity but overexpression raised it 7-fold. Overexpression-based evidence for the activity; correct. Supporting Evidence: PMID:17726007 Deletion of LPT1 had a minimal effect on 1-acyl-sn-glycerol-3-phosphate acyltransferase activity, but overexpression increased activity 7-fold. |
| GO:0005783 endoplasmic reticulum | HDA PMID:14562095 Global analysis of protein localization in budding yeast. | ACCEPT | Summary: Huh et al. 2003 GFP survey localised Ale1 to the ER. Consistent with MBOAT-family ER enzymes and with low-throughput GFP data (PMID:17890783). |
| GO:0005783 endoplasmic reticulum | HDA PMID:26928762 One library to make them all: streamlining the creation of y... | ACCEPT | Summary: Yofe et al. 2016 SWAT library high-throughput localisation: ER. Consistent with other evidence. |
| GO:0005783 endoplasmic reticulum | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT is_active_in ER from the fungal LPLAT node grounded on Ale1 itself. Correct. |
| GO:0005783 endoplasmic reticulum | IDA PMID:17890783 LPT1 encodes a membrane-bound O-acyltransferase involved in ... | ACCEPT | Summary: Lpt1-GFP localised to the ER (Tamaki et al. 2007). Correct. Supporting Evidence: PMID:17890783 An Lpt1-green fluorescent protein fusion protein localized at the endoplasmic reticulum. |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:14562095 Global analysis of protein localization in budding yeast. | ACCEPT | Summary: ER membrane, curated from the Huh et al. 2003 ER localisation plus the multi-pass MBOAT topology. Correct and more precise than ER. |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:17890783 LPT1 encodes a membrane-bound O-acyltransferase involved in ... | ACCEPT | Summary: ER membrane from the Lpt1-GFP ER localisation of a membrane-bound O-acyltransferase. Correct; core location. Supporting Evidence: PMID:17890783 An Lpt1-green fluorescent protein fusion protein localized at the endoplasmic reticulum. |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000120 | ACCEPT | Summary: ARBA/UniProt SubCell (SL-0097 ER membrane) mapping. Correct. |
| GO:0006644 phospholipid metabolic process | IEA GO_REF:0000041 | TOO GENERAL | Summary: UniPathway UPA00085 (phospholipid metabolism) mapping. Correct but very broad; the specific biosynthetic and remodeling processes are annotated separately. |
| GO:0006646 phosphatidylethanolamine biosynthetic process | IMP PMID:17652094 Identification and characterization of the major lysophospha... | ACCEPT | Summary: Riekhof et al. 2007: in strains lacking the Psd and Kennedy routes to PE, viability requires exogenous lyso-PE and functional ALE1, i.e. Ale1 acylates lyso-PE to PE. Ale1 performs the final acylation step, so participation is direct. Supporting Evidence: PMID:17652094 strains lacking the capacity for PtdEtn synthesis via the phosphatidylserine decarboxylase and Kennedy pathways show a stringent requirement for both exogenous lyso-PtdEtn and a functional ALE1 gene for viability |
| GO:0006656 phosphatidylcholine biosynthetic process | IGI PMID:30514764 The glycerophosphocholine acyltransferase Gpc1 is part of a ... | ACCEPT | Summary: Anaokar et al. 2019: Gpc1 acylates GPC to LPC and Ale1 converts LPC to PC in the PC deacylation/reacylation pathway; ale1 and gpc1 deletions reduce labelled PC. Ale1 catalyses the second acylation step, so its role in PC synthesis via this route is direct; the acts_upstream_of_or_within qualifier is conservative but acceptable. Supporting Evidence: PMID:30514764 These results confirm the formation of the immediate product of Gpc1 activity, LPC, in vivo , and the role of Ale1 in converting LPC into PC. |
| GO:0016020 membrane | IBA GO_REF:0000033 | TOO GENERAL | Summary: PAINT is_active_in membrane from the broad MBOAT/LPLAT node (PTN000357522). Correct but uninformative relative to ER membrane. |
| GO:0016747 acyltransferase activity, transferring groups other than amino-acyl groups | IDA PMID:17890783 LPT1 encodes a membrane-bound O-acyltransferase involved in ... | MODIFY | Summary: Tamaki et al. identified YOR175c in a deletion screen as the single mutant defective in acetyl-CoA:lyso-PAF acetyltransferase activity and showed Lpt1 acylates many lysophospholipids. The generic 'acyltransferase, transferring groups other than amino-acyl groups' is an uninformative grouping term; the lyso-PAF acetyltransferase activity has a specific term (1-alkylglycerophosphocholine O-acetyltransferase activity, EC 2.3.1.67), and the lysophospholipid acyltransferase activities are already annotated individually. Proposed replacements: 1-alkylglycerophosphocholine O-acetyltransferase activity Supporting Evidence: PMID:17890783 revealed a single mutant strain, YOR175c, with a defect in lysoPAF AT activity |
| GO:0016747 acyltransferase activity, transferring groups other than amino-acyl groups | IMP PMID:17890783 LPT1 encodes a membrane-bound O-acyltransferase involved in ... | MODIFY | Summary: Mutant evidence from the same deletion screen: the YOR175c deletion lacks lyso-PAF acetyltransferase activity. Replace the generic parent with the specific lyso-PAF acetyltransferase term. Proposed replacements: 1-alkylglycerophosphocholine O-acetyltransferase activity Supporting Evidence: PMID:17890783 revealed a single mutant strain, YOR175c, with a defect in lysoPAF AT activity |
| GO:0030258 lipid modification | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT inheritance of 'lipid modification' from the MBOAT LPLAT node (Drosophila and mammalian MBOATs). Ale1's re-acylation of lysolipids is a lipid modification, but the term is vague; the specific phospholipid biosynthesis and acyl-chain remodeling processes are better. |
| GO:0036151 phosphatidylcholine acyl-chain remodeling | IMP PMID:39730635 Acyl-CoA: lysophosphatidylcholine acyltransferase from diato... | ACCEPT | Summary: Study of diatom PtLPCAT1 in a yeast ale1 background, also testing yeast ALE1 overexpression: Ale1 can remodel microsomal PC acyl chains (lower intensity than the plant/diatom enzymes). Consistent with Ale1 being the main LPCAT; accept as PC acyl-chain remodeling. Supporting Evidence: PMID:39730635 The results have shown that Arabidopsis AtLPCAT1 possesses an even higher ability to remodel such a PC than diatom PtLPCAT1 and that yeast ALE1 can remodel it also, however, with a lower intensity (Fig. 3) |
| GO:0044233 mitochondria-associated endoplasmic reticulum membrane contact site | IDA PMID:17652094 Identification and characterization of the major lysophospha... | ACCEPT | Summary: Riekhof et al. 2007 found Ale1 highly enriched in the mitochondria-associated ER membrane (MAM) fraction. Correct, a sub-domain of its ER membrane localisation. Supporting Evidence: PMID:17652094 highly enriched in the mitochondria-associated endoplasmic reticulum membrane |
| GO:0044233 mitochondria-associated endoplasmic reticulum membrane contact site | IDA PMID:38297966 Mlg1, a yeast acyltransferase located in ER membranes associ... | ACCEPT | Summary: Laquel et al. 2024 (Mlg1 study) used subcellular fractionation of MAMs; Ale1 is reported in this fraction (abstract-only cache; curator read full text). Consistent with Riekhof et al. 2007. |
| GO:0046474 glycerophospholipid biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT node grounded on yeast/Candida ALE1. Correct: Ale1 acylates lysophospholipids to make PA, PC and PE. |
| GO:0046474 glycerophospholipid biosynthetic process | IGI PMID:17675291 SLC1 and SLC4 encode partially redundant acyl-coenzyme A 1-a... | ACCEPT | Summary: slc1 slc4(ale1) synthetic lethality and altered glycerophospholipid profiles show Ale1 makes glycerophospholipids with Slc1. Correct. Supporting Evidence: PMID:17675291 The simultaneous deletion of SLC1 and SLC4 is lethal. |
| GO:0046474 glycerophospholipid biosynthetic process | IMP PMID:17675291 SLC1 and SLC4 encode partially redundant acyl-coenzyme A 1-a... | ACCEPT | Summary: Lipid profiling of slc4 (ale1) cells (Benghezal et al. 2007). Correct. Supporting Evidence: PMID:17675291 Mass spectrometric analysis of lipids from slc1Delta and slc4Delta cells demonstrates that in vivo Slc1p and Slc4p generate almost the same glycerophospholipid profile. |
| GO:0046474 glycerophospholipid biosynthetic process | IMP PMID:17726007 Identification of a novel lysophospholipid acyltransferase i... | ACCEPT | Summary: Pulse-labelling of lpt1 cells showed reduced oleate incorporation into PC. Correct. Supporting Evidence: PMID:17726007 Pulse-labeling of lpt1Delta strains showed a 30% reduction in [3H]oleate incorporation into phosphatidylcholine only. |
| GO:0046474 glycerophospholipid biosynthetic process | IMP PMID:17890783 LPT1 encodes a membrane-bound O-acyltransferase involved in ... | ACCEPT | Summary: Lyso-PC and lyso-PE accumulate in lpt1 mutants (Tamaki et al. 2007). Correct. Supporting Evidence: PMID:17890783 A liquid chromatography-mass spectrometry analysis indicated that lysophosphatidylcholine and lysophosphatidylethanolamine accumulated in the Deltalpt1 mutant strain. |
| GO:0047184 1-acylglycerophosphocholine O-acyltransferase activity | EXP PMID:17890783 LPT1 encodes a membrane-bound O-acyltransferase involved in ... | ACCEPT | Summary: Lpt1 acylates lysophosphatidylcholine among many lysophospholipids. Correct; LPCAT is Ale1's preferred activity. |
| GO:0047184 1-acylglycerophosphocholine O-acyltransferase activity | EXP PMID:26643989 Possible Role of Different Yeast and Plant Lysophospholipid:... | ACCEPT | Summary: Ale1 showed its highest activity toward lysoPtdCho (about 10 times AtLPCAT2). Correct; core MF. Supporting Evidence: PMID:26643989 Ale1 also showed broad acyl specificity, having high activities towards lysoPtdCho, lysoPtdOH, and lysoPtdEtn with highest activity towards lysoPtdCho (Fig. 1d). |
| GO:0047184 1-acylglycerophosphocholine O-acyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT LPCAT inheritance on the fungal LPLAT node, grounded on Ale1. Sound. |
| GO:0047184 1-acylglycerophosphocholine O-acyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: RHEA:12937/RHEA:35991 and EC 2.3.1.23 mapping. Correct. |
| GO:0047184 1-acylglycerophosphocholine O-acyltransferase activity | IMP PMID:17726007 Identification of a novel lysophospholipid acyltransferase i... | ACCEPT | Summary: LPT1 deletion abrogated esterification of other lysophospholipids and overexpression raised LPCAT activity 7-fold. Correct. Supporting Evidence: PMID:17726007 Deletion of LPT1 abrogated the esterification of other lysophospholipids, and overexpression increased lysophosphatidylcholine acyltransferase activity 7-fold. |
| GO:0047184 1-acylglycerophosphocholine O-acyltransferase activity | IMP PMID:17951629 Lysophosphatidylcholine metabolism in Saccharomyces cerevisi... | ACCEPT | Summary: Riekhof et al. 2007b: after lyso-PC import, Ale1 is the sole lyso-PC acyltransferase in yeast. Correct; core MF. Supporting Evidence: PMID:17951629 After import of lyso-PtdCho, the recently characterized lyso-PtdEtn acyltransferase, Ale1p, functioned as the sole lyso-PtdCho acyltransferase in yeast. |
| GO:0071618 lysophosphatidylethanolamine acyltransferase activity | IDA PMID:17652094 Identification and characterization of the major lysophospha... | ACCEPT | Summary: Ale1 encodes the major acyl-CoA-dependent LPEAT activity, with a strong preference for unsaturated acyl-CoA. Correct; overlaps GO:0106262 (the acyl-CoA-dependent 1-acylglycerophosphoethanolamine O-acyltransferase). Supporting Evidence: PMID:17652094 Ale1p catalytic activity has a pH optimum between pH 7 and 7.5 and a strong preference for unsaturated acyl-CoA substrates. |
| GO:0071618 lysophosphatidylethanolamine acyltransferase activity | IMP PMID:17652094 Identification and characterization of the major lysophospha... | ACCEPT | Summary: ale1 deletion leaves only trace acyl-CoA-dependent LPEAT activity. Correct. Supporting Evidence: PMID:17652094 An ale1Delta strain retains only trace amounts of acyl-CoA-dependent LPEAT activity |
| GO:0106262 1-acylglycerophosphoethanolamine O-acyltransferase activity | EXP PMID:17890783 LPT1 encodes a membrane-bound O-acyltransferase involved in ... | ACCEPT | Summary: Lpt1 acylates lysophosphatidylethanolamine with acyl-CoA. Correct. |
| GO:0106262 1-acylglycerophosphoethanolamine O-acyltransferase activity | EXP PMID:26643989 Possible Role of Different Yeast and Plant Lysophospholipid:... | ACCEPT | Summary: High activity toward oleoyl-lysoPtdEtn in ale1 microsomes expressing Ale1. Correct. Supporting Evidence: PMID:26643989 Ale1 also showed broad acyl specificity, having high activities towards lysoPtdCho, lysoPtdOH, and lysoPtdEtn with highest activity towards lysoPtdCho (Fig. 1d). |
| GO:0106262 1-acylglycerophosphoethanolamine O-acyltransferase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Rhea (RHEA:32995/RHEA:37499) mapping from UniProt catalytic activity. Correct. |
| GO:0106263 1-acylglycerophosphoserine O-acyltransferase activity | EXP PMID:17890783 LPT1 encodes a membrane-bound O-acyltransferase involved in ... | KEEP AS NON CORE | Summary: Lpt1 also acylates lysophosphatidylserine (Tamaki et al. 2007; also Riekhof et al. 2007b). A real but minor activity of a broad-specificity enzyme; non-core. Supporting Evidence: PMID:17951629 In addition to lyso-PtdCho, lyso-PtdEtn, and lyso-phosphatidic acid, Ale1p was also active with lysophosphatidylserine, lysophosphatidylglycerol, and lysophosphatidylinositol as substrates. |
| GO:0106263 1-acylglycerophosphoserine O-acyltransferase activity | IEA GO_REF:0000116 | KEEP AS NON CORE | Summary: Rhea (RHEA:33191/RHEA:37407) mapping. Correct but a minor substrate; non-core. |
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Download this section (compressed HTML)Q: How much of in vivo PA synthesis for triacylglycerol, as opposed to phospholipid remodeling, is carried out by Ale1 in wild-type cells where Slc1 is present?
Q: Does the MAM enrichment of Ale1 channel PE or PC to mitochondria, and is it regulated by growth conditions?
Q: Is lyso-PAF acetyltransferase activity physiologically relevant in yeast or an in vitro side activity of the broad-specificity MBOAT?
Experiment: Quantify flux of [14C]glycerol-3-phosphate into PA, PC and TAG in slc1 versus ale1 conditional mutants to define the in vivo share of Ale1 in de novo PA synthesis.
Type: metabolic labeling
Broad-specificity lysophospholipid acyltransferase; major lysophosphatidylethanolamine acyltransferase that localizes to the mitochondria-associated ER membrane; member of the MBOAT family of membrane-bound O-acyltransferases; key component of Lands cycle; capable of remodeling phosphatidylcholine containing VLC polyunsaturated fatty acids and involved in fatty acid exchange at the sn-2 position of mature glycerophospholipids
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