LRO1 encodes phospholipid:diacylglycerol acyltransferase (PDAT; EC 2.3.1.158), an LCAT-related enzyme of the alpha/beta-hydrolase (lipase) superfamily. It makes triacylglycerol without acyl-CoA by transferring the sn-2 acyl chain of a glycerophospholipid (mainly phosphatidylethanolamine or phosphatidylcholine) to 1,2-diacylglycerol, which also releases an sn-1 lysophospholipid. With the acyl-CoA-dependent DGAT Dga1 it accounts for most TAG synthesis, and it is the major TAG synthase in exponentially growing cells. Lro1 is a single-pass type II ER membrane protein with its catalytic domain in the ER lumen. It concentrates at seipin/Nem1-defined ER subdomains where lipid droplets form, and on nutrient depletion it relocates to a subdomain of the inner nuclear membrane, where its TAG synthesis remodels nuclear membrane phospholipids. In vitro it can use a broad range of acyl donors and acceptors, and it can acylate ceramides to 1-O-acylceramides.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005637 nuclear inner membrane | IDA PMID:31422915 Compartmentalized Synthesis of Triacylglycerol at the Inner ... | ACCEPT | Summary: IDA from Barbosa et al. 2019; Lro1 relocates from the ER to a subdomain of the inner nuclear membrane on nutrient depletion and is active there. Supporting Evidence: PMID:31422915 Lro1, an acyltransferase that generates TGs from phospholipid-derived FAs in yeast, relocates from the endoplasmic reticulum to a subdomain of the inner nuclear membrane PMID:31422915 Lro1 is active at this specific nuclear subdomain resulting in the utilization of phospholipid-derived fatty acids to generate TGs and lysophospholipids. |
| GO:0005637 nuclear inner membrane | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from UniProt subcellular location (SL-0179 nucleus inner membrane), based on PMID:31422915. Correct. Supporting Evidence: PMID:31422915 Lro1, an acyltransferase that generates TGs from phospholipid-derived FAs in yeast, relocates from the endoplasmic reticulum to a subdomain of the inner nuclear membrane |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT IBA (is_active_in cytoplasm) at the PDAT node, grounded in S. cerevisiae Lro1 and S. pombe Plh1. Reason: Very general; Lro1's catalytic domain is in the ER lumen, so ER membrane and nuclear inner membrane are the informative locations. Retained as a coarse non-core location. Supporting Evidence: file:yeast/LRO1/LRO1-uniprot.txt type II membrane protein {ECO:0000269|PubMed:22446555} |
| GO:0005783 endoplasmic reticulum | HDA PMID:26928762 One library to make them all: streamlining the creation of y... | ACCEPT | Summary: HDA from the SWAT N-terminal GFP endomembrane library (Yofe et al. 2016) (ER). Supporting Evidence: PMID:26928762 carrying SWAT-GFP modules at the amino termini of endomembrane proteins PMID:31422915 Lro1-GFP localizes to the ER during the exponential growth phase (EXP) |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:22454508 The ubiquitin-like (UBX)-domain-containing protein Ubx2/Ubxd... | ACCEPT | Summary: SGD EXP from Wang and Lee 2012; Lro1 moves along the ER and concentrates at LD assembly sites. Supporting Evidence: PMID:22454508 phospholipid:diacylglycerol acyltransferase (Lro1), one of the two TAG-synthesizing enzymes in yeast, which moves along the ER and distributes dynamically to the putative LD assembly sites abutting LDs |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:31422915 Compartmentalized Synthesis of Triacylglycerol at the Inner ... | ACCEPT | Summary: SGD EXP from Barbosa et al. 2019; Lro1-GFP is ER-localised in exponential phase. Supporting Evidence: PMID:31422915 Lro1-GFP localizes to the ER during the exponential growth phase (EXP) |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:32349126 Seipin and Nem1 establish discrete ER subdomains to initiate... | ACCEPT | Summary: SGD EXP from Choudhary et al. 2020; Lro1 is recruited to seipin/Nem1 ER subdomains where droplets form. Supporting Evidence: PMID:32349126 LDs induced by the yeast triacylglycerol (TAG)-synthases Lro1 and Dga1 are formed at discrete ER subdomains defined by seipin (Fld1) |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from UniProt subcellular location (SL-0097 ER membrane). Correct. Supporting Evidence: file:yeast/LRO1/LRO1-uniprot.txt type II membrane protein {ECO:0000269|PubMed:22446555} |
| GO:0005811 lipid droplet | IDA PMID:22454508 The ubiquitin-like (UBX)-domain-containing protein Ubx2/Ubxd... | KEEP AS NON CORE | Summary: IDA (lipid droplet) from Wang and Lee 2012, who describe Lro1 distributing to ER sites abutting lipid droplets. Reason: As a single-pass type II ER membrane protein, Lro1 is better described as sitting at ER-LD contact and droplet-assembly sites than on the droplet monolayer. Retained as non-core on the curator's authority. Supporting Evidence: PMID:22454508 phospholipid:diacylglycerol acyltransferase (Lro1), one of the two TAG-synthesizing enzymes in yeast, which moves along the ER and distributes dynamically to the putative LD assembly sites abutting LDs |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: YeastPathways RCA placing the PDAT step of TRIGLSYN-PWY in the cytosol. Reason: Lro1 is a type II ER membrane protein whose catalytic domain lies in the ER lumen. The cytosol location is a pathway default that contradicts the established topology. Supporting Evidence: file:yeast/LRO1/LRO1-uniprot.txt type II membrane protein {ECO:0000269|PubMed:22446555} PMID:22454508 phospholipid:diacylglycerol acyltransferase (Lro1), one of the two TAG-synthesizing enzymes in yeast, which moves along the ER and distributes dynamically to the putative LD assembly sites abutting LDs |
| GO:0006629 lipid metabolic process | IEA GO_REF:0000002 | TOO GENERAL | Summary: IEA from InterPro IPR003386 (LCAT family) for lipid metabolic process. Correct but general. Supporting Evidence: PMID:10829075 The encoded PDAT protein is related to lecithin:cholesterol acyltransferase, which catalyzes the acyl-CoA-independent synthesis of cholesterol esters. |
| GO:0006672 ceramide metabolic process | IDA PMID:22738231 A novel pathway of ceramide metabolism in Saccharomyces cere... | KEEP AS NON CORE | Summary: IDA from Voynova et al. 2012; immunopurified Lro1 acylated NBD-ceramide at the C1 hydroxyl to make 1-O-acylceramide. Reason: Genuine but minor side activity on ceramide; the core role is TAG synthesis. Supporting Evidence: PMID:22738231 Immunopurified Lro1p was equally able to acylate NBD-ceramide. |
| GO:0006672 ceramide metabolic process | IMP PMID:22738231 A novel pathway of ceramide metabolism in Saccharomyces cere... | KEEP AS NON CORE | Summary: IMP from Voynova et al. 2012; acylceramide synthesis in vivo depended on Lro1 and Dga1. Reason: Non-core side reaction. Supporting Evidence: PMID:22738231 Its biosynthesis was dependent on the diacylglycerol acyltransfereases Lro1p and Dga1p |
| GO:0016747 acyltransferase activity, transferring groups other than amino-acyl groups | IEA GO_REF:0000002 | TOO GENERAL | Summary: IEA from InterPro IPR003386 for acyltransferase activity, transferring groups other than amino-acyl groups. A correct general parent of PDAT activity. Supporting Evidence: PMID:10829075 The encoded PDAT protein is related to lecithin:cholesterol acyltransferase, which catalyzes the acyl-CoA-independent synthesis of cholesterol esters. |
| GO:0019432 triglyceride biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for triglyceride biosynthetic process at the PDAT node (Lro1, S. pombe Plh1). Correct. Supporting Evidence: PMID:10829075 budding yeast PDAT and its relatives in fission yeast and Arabidopsis form a distinct branch within this protein superfamily |
| GO:0019432 triglyceride biosynthetic process | IDA PMID:10747858 A lecithin cholesterol acyltransferase-like gene mediates di... | ACCEPT | Summary: IDA from Oelkers et al. 2000; microsomal assays showed Lro1-dependent esterification of DAG using PC as acyl donor. Supporting Evidence: PMID:10747858 In vitro microsomal assays determined that Lro1 mediated the esterification of diacylglycerol using phosphatidylcholine as the acyl donor. |
| GO:0019432 triglyceride biosynthetic process | IEA GO_REF:0000117 | ACCEPT | Summary: IEA from ARBA rule ARBA00026657 for triglyceride biosynthetic process. Correct. Supporting Evidence: PMID:10747858 deletion of LRO1, a homolog of human lecithin cholesterol acyltransferase, resulted in a dramatic reduction in triglyceride synthesis, whereas overexpression of LRO1 yielded a significant increase in triglyceride production |
| GO:0019432 triglyceride biosynthetic process | IMP PMID:10747858 A lecithin cholesterol acyltransferase-like gene mediates di... | ACCEPT | Summary: IMP from Oelkers et al. 2000; lro1 deletion dramatically reduced triglyceride synthesis. Supporting Evidence: PMID:10747858 deletion of LRO1, a homolog of human lecithin cholesterol acyltransferase, resulted in a dramatic reduction in triglyceride synthesis, whereas overexpression of LRO1 yielded a significant increase in triglyceride production |
| GO:0019432 triglyceride biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (TRIGLSYN-PWY) for triglyceride biosynthetic process. Correct. Supporting Evidence: PMID:10747858 deletion of LRO1, a homolog of human lecithin cholesterol acyltransferase, resulted in a dramatic reduction in triglyceride synthesis, whereas overexpression of LRO1 yielded a significant increase in triglyceride production |
| GO:0019915 lipid storage | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT IBA for lipid storage at the PDAT node. Reason: Lro1 makes storage TAG, so it takes part in storage, but the specific role is TAG synthesis (GO:0019432). Keep as a broader, non-core process. Supporting Evidence: PMID:10747858 deletion of LRO1, a homolog of human lecithin cholesterol acyltransferase, resulted in a dramatic reduction in triglyceride synthesis, whereas overexpression of LRO1 yielded a significant increase in triglyceride production |
| GO:0019915 lipid storage | IDA PMID:10747858 A lecithin cholesterol acyltransferase-like gene mediates di... | KEEP AS NON CORE | Summary: IDA from Oelkers et al. 2000 for lipid storage (TAG formation). Reason: As above; TAG biosynthesis is the specific process. Supporting Evidence: PMID:10747858 deletion of LRO1, a homolog of human lecithin cholesterol acyltransferase, resulted in a dramatic reduction in triglyceride synthesis, whereas overexpression of LRO1 yielded a significant increase in triglyceride production |
| GO:0019915 lipid storage | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IEA from ARBA rule ARBA00028621 for lipid storage. Reason: As above; broader non-core process. Supporting Evidence: PMID:10747858 deletion of LRO1, a homolog of human lecithin cholesterol acyltransferase, resulted in a dramatic reduction in triglyceride synthesis, whereas overexpression of LRO1 yielded a significant increase in triglyceride production |
| GO:0019915 lipid storage | IMP PMID:10747858 A lecithin cholesterol acyltransferase-like gene mediates di... | KEEP AS NON CORE | Summary: IMP from Oelkers et al. 2000; lro1 deletion reduced TAG synthesis and overexpression increased it. Reason: As above; broader non-core process. Supporting Evidence: PMID:10747858 deletion of LRO1, a homolog of human lecithin cholesterol acyltransferase, resulted in a dramatic reduction in triglyceride synthesis, whereas overexpression of LRO1 yielded a significant increase in triglyceride production |
| GO:0046027 phospholipid:diacylglycerol acyltransferase activity | EXP PMID:18037386 Saccharomyces cerevisiae phospholipid:diacylglycerol acyl tr... | ACCEPT | Summary: SGD EXP from Ghosal et al. 2007; a soluble, N-terminally truncated Lro1 secreted from Pichia retained PDAT activity, preferring sn-2 acyl groups of PE as donor and 1,2-DAG as acceptor. Supporting Evidence: PMID:18037386 the highest activity was achieved with acyl groups at sn-2 position of phosphatidylethanolamine as acyl donor and 1,2-diacylglycerols as acyl acceptor |
| GO:0046027 phospholipid:diacylglycerol acyltransferase activity | EXP PMID:30706417 Expanding of Phospholipid:Diacylglycerol AcylTransferase (PD... | ACCEPT | Summary: SGD EXP from Feng et al. 2019; purified ScPDAT uses PE and PC preferentially, plus a broad range of other acyl donors. Supporting Evidence: PMID:30706417 In addition of the preferred acyl donor of PE and PC, the results identified that ScPDAT was capable of using broad acyl donors |
| GO:0046027 phospholipid:diacylglycerol acyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for PDAT activity at the fungal/plant PDAT node, grounded in Lro1 and S. pombe Plh1. Correct. Supporting Evidence: PMID:10829075 budding yeast PDAT and its relatives in fission yeast and Arabidopsis form a distinct branch within this protein superfamily |
| GO:0046027 phospholipid:diacylglycerol acyltransferase activity | IDA PMID:10747858 A lecithin cholesterol acyltransferase-like gene mediates di... | ACCEPT | Summary: IDA from Oelkers et al. 2000; microsomal assays showed Lro1-mediated DAG esterification using PC. Supporting Evidence: PMID:10747858 In vitro microsomal assays determined that Lro1 mediated the esterification of diacylglycerol using phosphatidylcholine as the acyl donor. |
| GO:0046027 phospholipid:diacylglycerol acyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA from RHEA/EC 2.3.1.158 mapping derived from UniProt's PDAT reaction. Correct. Supporting Evidence: file:yeast/LRO1/LRO1-uniprot.txt Reaction=a glycerophospholipid + a 1,2-diacyl-sn-glycerol = a |
| GO:0046027 phospholipid:diacylglycerol acyltransferase activity | IMP PMID:10829075 Phospholipid:diacylglycerol acyltransferase: an enzyme that ... | ACCEPT | Summary: IMP from Dahlqvist et al. 2000, who discovered PDAT and identified the yeast gene (LRO1) by mutant analysis. Supporting Evidence: PMID:10829075 This reaction is catalyzed by an enzyme that we call phospholipid:diacylglycerol acyltransferase, or PDAT. PMID:10829075 We further found that PDAT activity also is present in yeast microsomes. |
| GO:0046027 phospholipid:diacylglycerol acyltransferase activity | ISO PMID:10829075 Phospholipid:diacylglycerol acyltransferase: an enzyme that ... | REMOVE | Summary: ISO from CACAO, citing PMID:10829075 with mouse LCAT (UniProtKB:P16301) as the source. LCAT is a phosphatidylcholine:sterol O-acyltransferase, not a PDAT. Reason: The source entity does not have PDAT activity, so this transfer is mis-sourced. The conclusion itself (Lro1 has PDAT activity) is correct and is fully covered by the IDA, IMP, EXP and IBA rows. Removing this row loses no information. Dahlqvist et al. note that PDAT forms a branch distinct from LCAT. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG Sources checked: UniProtKB:P16301 · Lcat (Mus musculus) NOT RELEVANT Mouse LCAT is a phosphatidylcholine-sterol acyltransferase in a distinct branch of the LCAT/PDAT superfamily; it is not a phospholipid:diacylglycerol acyltransferase. Supporting Evidence: PMID:10829075 budding yeast PDAT and its relatives in fission yeast and Arabidopsis form a distinct branch within this protein superfamily PMID:10829075 The encoded PDAT protein is related to lecithin:cholesterol acyltransferase, which catalyzes the acyl-CoA-independent synthesis of cholesterol esters. |
| GO:0046027 phospholipid:diacylglycerol acyltransferase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (TRIGLSYN-PWY) assigning the PC + DAG -> TAG + lyso-PC step (EC 2.3.1.158) to Lro1. Correct. Supporting Evidence: PMID:10747858 In vitro microsomal assays determined that Lro1 mediated the esterification of diacylglycerol using phosphatidylcholine as the acyl donor. |
| GO:0055091 phospholipid homeostasis | IDA PMID:31422915 Compartmentalized Synthesis of Triacylglycerol at the Inner ... | KEEP AS NON CORE | Summary: IDA from Barbosa et al. 2019; Lro1 activity at the inner nuclear membrane consumes phospholipid acyl chains, affecting membrane phospholipid homeostasis and nuclear integrity. Reason: A downstream consequence of PDAT activity (phospholipid acyl chains drawn into TAG) rather than a separate homeostatic function; non-core. Supporting Evidence: PMID:31422915 Lro1 Activity Regulates Phospholipid Homeostasis PMID:31422915 Lro1 is active at this specific nuclear subdomain resulting in the utilization of phospholipid-derived fatty acids to generate TGs and lysophospholipids. |
| GO:0097038 perinuclear endoplasmic reticulum | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA (is_active_in perinuclear ER) at the PDAT node. Consistent with Lro1 localisation. Supporting Evidence: PMID:22454508 phospholipid:diacylglycerol acyltransferase (Lro1), one of the two TAG-synthesizing enzymes in yeast, which moves along the ER and distributes dynamically to the putative LD assembly sites abutting LDs PMID:31422915 Lro1, an acyltransferase that generates TGs from phospholipid-derived FAs in yeast, relocates from the endoplasmic reticulum to a subdomain of the inner nuclear membrane |
| GO:0097038 perinuclear endoplasmic reticulum | IDA PMID:22454508 The ubiquitin-like (UBX)-domain-containing protein Ubx2/Ubxd... | ACCEPT | Summary: IDA from Wang and Lee 2012, who imaged Lro1 in perinuclear ER and at LD assembly sites. Supporting Evidence: PMID:22454508 phospholipid:diacylglycerol acyltransferase (Lro1), one of the two TAG-synthesizing enzymes in yeast, which moves along the ER and distributes dynamically to the putative LD assembly sites abutting LDs |
| GO:0097038 perinuclear endoplasmic reticulum | IEA GO_REF:0000117 | ACCEPT | Summary: IEA from ARBA rule ARBA00090299 for perinuclear ER. Correct. Supporting Evidence: PMID:22454508 phospholipid:diacylglycerol acyltransferase (Lro1), one of the two TAG-synthesizing enzymes in yeast, which moves along the ER and distributes dynamically to the putative LD assembly sites abutting LDs |
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Download this section (compressed HTML)Q: Is the lysophospholipid released by Lro1 re-acylated locally (by Ale1/Slc1) or does it signal, and how does this coupling affect nuclear membrane expansion?
Q: Which signals (Lro1 Ser-324 phosphorylation, nutrient status) target Lro1 to the inner nuclear membrane subdomain?
Experiment: Track lysophospholipid and TAG production at the inner nuclear membrane using INM-anchored versus ER-anchored Lro1 in an ale1 or slc1 background, with lipidomics of purified nuclear envelopes.
Hypothesis: Lro1-generated lysophospholipids are re-acylated locally, coupling TAG synthesis to nuclear membrane remodelling.
Type: lipidomics/cell biology
Acyltransferase that converts diacylglycerol to triacylglycerol (TGA); one of several acyltransferases that contribute to TGA synthesis; relocates from ER to nuclear membrane in response cell cycle and starvation signals; Lro1p and Dga1p can O-acylate ceramides; putative homolog of human lecithin cholesterol acyltransferase
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