LPP1 encodes a Mg2+-independent lipid phosphate phosphatase of the PAP2 (lipid phosphate phosphatase) superfamily and is the paralogue of the vacuolar DGPP phosphatase Dpp1. It is an integral multi-pass membrane protein of the Golgi. Lpp1 dephosphorylates phosphatidate (PA) to diacylglycerol, and also hydrolyses lysophosphatidate (LPA) and diacylglycerol pyrophosphate (DGPP). PA is its preferred substrate; activity measurements in the gene-identification study ranked PA > LPA > DGPP, and specificity constants of the overexpressed enzyme also rank PA first, with LPA lowest. It is unusually sensitive to N-ethylmaleimide. Together with Dpp1 it accounts for nearly all Mg2+-independent PA and LPA phosphatase activity and contributes to hydrolysis of isoprenoid phosphates. lpp1 and dpp1 lpp1 mutants grow normally but have altered cellular PA and phosphatidylinositol levels. Lpp1 is not the main source of diacylglycerol for triacylglycerol synthesis, which depends on the Mg2+-dependent lipin Pah1.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000139 Golgi membrane | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from UniProt subcellular location (SL-0134 Golgi apparatus membrane), which UniProt bases on the Huh et al. GFP survey. Consistent with the literature describing Lpp1 as a Golgi enzyme. Supporting Evidence: file:yeast/LPP1/LPP1-uniprot.txt SUBCELLULAR LOCATION: Golgi apparatus membrane PMID:24196957 are integral membrane enzymes that are localized to the vacuole and Golgi compartments, respectively |
| GO:0000810 diacylglycerol diphosphate phosphatase activity | EXP PMID:10685032 Enzymological properties of the LPP1-encoded lipid phosphata... | ACCEPT | Summary: SGD EXP from Furneisen and Carman 2000; Lpp1 overexpressed in insect cells dephosphorylated DGPP with saturation kinetics. Supporting Evidence: PMID:10685032 The product of the LPP1 gene in Saccharomyces cerevisiae is a membrane-associated enzyme that catalyzes the Mg(2+)-independent dephosphorylation of phosphatidate (PA), diacylglycerol pyrophosphate (DGPP), and lysophosphatidate (LPA). PMID:10685032 The LPP1-encoded enzyme exhibited saturation kinetics with respect to the surface concentrations of PA (K(m)=0.05 mol%), DGPP (K(m)=0.07 mol%), and LPA (K(m)=0.08 mol%). |
| GO:0000810 diacylglycerol diphosphate phosphatase activity | EXP PMID:9603941 Isolation and characterization of the Saccharomyces cerevisi... | ACCEPT | Summary: SGD EXP from Toke et al. 1998 (gene identification); the LPP1 product showed DGPP phosphatase activity in addition to PA and LPA phosphatase. Supporting Evidence: PMID:9603941 The LPP1 gene product also exhibited lyso-PA phosphatase and DGPP phosphatase activities. |
| GO:0000810 diacylglycerol diphosphate phosphatase activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA from RHEA/EC 3.6.1.75 mapping derived from UniProt's DGPP phosphatase reaction for Lpp1. Correct, although DGPP is its least preferred substrate. Supporting Evidence: file:yeast/LPP1/LPP1-uniprot.txt Reaction=a 1,2-diacyl-sn-glycerol 3-diphosphate + H2O = a 1,2-diacyl- |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: YeastPathways RCA placing Lpp1's PA phosphatase step of TRIGLSYN-PWY in the cytosol. Lpp1 is an integral Golgi membrane protein. Reason: The cytosol location is a pathway default that contradicts the membrane localisation of this multi-pass enzyme, whose activity fractionates with membranes. Supporting Evidence: PMID:9603941 The Mg2+-independent PA phosphatase activity encoded by the LPP1 gene was associated with the membrane fraction of the cell. PMID:24196957 are integral membrane enzymes that are localized to the vacuole and Golgi compartments, respectively |
| GO:0006629 lipid metabolic process | IEA GO_REF:0000117 | TOO GENERAL | Summary: IEA from ARBA rule ARBA00028591 for lipid metabolic process. Correct but very general. Supporting Evidence: PMID:10685032 The product of the LPP1 gene in Saccharomyces cerevisiae is a membrane-associated enzyme that catalyzes the Mg(2+)-independent dephosphorylation of phosphatidate (PA), diacylglycerol pyrophosphate (DGPP), and lysophosphatidate (LPA). |
| GO:0006644 phospholipid metabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for phospholipid metabolic process at the LPP family node (PTN000017950), grounded in Lpp1, Dpp1 and mammalian PLPP enzymes. Supporting Evidence: PMID:9603941 the LPP1 and DPP1 gene products played a role in the regulation of phospholipid metabolism and the cellular levels of phosphatidylinositol and PA |
| GO:0006644 phospholipid metabolic process | IEA GO_REF:0000002 | ACCEPT | Summary: IEA from InterPro IPR043216 (lipid phosphate phosphatase family) for phospholipid metabolic process. Correct for Lpp1. Supporting Evidence: file:yeast/LPP1/LPP1-uniprot.txt SIMILARITY: Belongs to the PA-phosphatase related phosphoesterase |
| GO:0006644 phospholipid metabolic process | IMP PMID:10329682 The LPP1 and DPP1 gene products account for most of the isop... | ACCEPT | Summary: IMP from Faulkner et al. 1999; lpp1 and dpp1 disruptions reduced Mg2+-independent PA and isoprenoid phosphate hydrolysis. Supporting Evidence: PMID:10329682 the disruption of DPP1 and LPP1 produced profound losses of Mg2+-independent PA phosphatase activity PMID:10329682 Disruption of either LPP1 or DPP1 caused respective decreases of about 25 and 75% in Mg2+-independent hydrolysis of several isoprenoid phosphates by particulate fractions isolated from these cells. |
| GO:0008195 phosphatidate phosphatase activity | EXP PMID:9603941 Isolation and characterization of the Saccharomyces cerevisi... | ACCEPT | Summary: SGD EXP from Toke et al. 1998; LPP1 overexpression in yeast and insect cells increased Mg2+-independent PA phosphatase activity, and PA was the preferred substrate. Supporting Evidence: PMID:9603941 The heterologous expression of the S. cerevisiae LPP1 gene in Sf-9 insect cells resulted in a 715-fold overexpression of Mg2+-independent PA phosphatase activity relative to control insect cells. PMID:9603941 The order of substrate preference was PA > lyso-PA > DGPP. |
| GO:0008195 phosphatidate phosphatase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for phosphatidate phosphatase activity at the LPP family node. Correct; Lpp1 is the experimentally grounded yeast member. Supporting Evidence: PMID:9603941 The order of substrate preference was PA > lyso-PA > DGPP. |
| GO:0008195 phosphatidate phosphatase activity | IDA PMID:10685032 Enzymological properties of the LPP1-encoded lipid phosphata... | ACCEPT | Summary: IDA from Furneisen and Carman 2000 enzymology of the LPP1-encoded PA phosphatase. Supporting Evidence: PMID:10685032 The product of the LPP1 gene in Saccharomyces cerevisiae is a membrane-associated enzyme that catalyzes the Mg(2+)-independent dephosphorylation of phosphatidate (PA), diacylglycerol pyrophosphate (DGPP), and lysophosphatidate (LPA). PMID:10685032 The LPP1-encoded enzyme exhibited saturation kinetics with respect to the surface concentrations of PA (K(m)=0.05 mol%), DGPP (K(m)=0.07 mol%), and LPA (K(m)=0.08 mol%). |
| GO:0008195 phosphatidate phosphatase activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA from RHEA/EC 3.1.3.4 mapping derived from UniProt's PA phosphatase reaction. Correct. Supporting Evidence: file:yeast/LPP1/LPP1-uniprot.txt Reaction=a 1,2-diacyl-sn-glycero-3-phosphate + H2O = a 1,2-diacyl-sn- |
| GO:0008195 phosphatidate phosphatase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (TRIGLSYN-PWY) assigning the PA -> DAG step (EC 3.1.3.4) to Lpp1. The MF is correct for Lpp1. Reason: The activity is real. Its contribution to TAG synthesis is small (see the BP row GO:0019432). Supporting Evidence: PMID:9603941 The order of substrate preference was PA > lyso-PA > DGPP. PMID:24196957 showed the essential role of PAH1 in triacylglycerol synthesis throughout growth |
| GO:0016020 membrane | IBA GO_REF:0000033 | TOO GENERAL | Summary: PAINT IBA (is_active_in membrane) for the LPP clade. Correct but general. Supporting Evidence: PMID:9603941 The Mg2+-independent PA phosphatase activity encoded by the LPP1 gene was associated with the membrane fraction of the cell. |
| GO:0016020 membrane | IDA PMID:10685032 Enzymological properties of the LPP1-encoded lipid phosphata... | TOO GENERAL | Summary: IDA from Furneisen and Carman 2000; Lpp1 is a membrane-associated enzyme. Supporting Evidence: PMID:10685032 The product of the LPP1 gene in Saccharomyces cerevisiae is a membrane-associated enzyme that catalyzes the Mg(2+)-independent dephosphorylation of phosphatidate (PA), diacylglycerol pyrophosphate (DGPP), and lysophosphatidate (LPA). |
| GO:0019432 triglyceride biosynthetic process | RCA GO_REF:0000123 | MARK AS OVER ANNOTATED | Summary: YeastPathways RCA placing Lpp1 in triglyceride biosynthesis (TRIGLSYN-PWY) because it can dephosphorylate PA. Reason: Pah1, the Mg2+-dependent lipin, supplies DAG for TAG synthesis throughout growth. Lpp1 is a Golgi Mg2+-independent lipid phosphate phosphatase with no reported TAG-synthesis role; lpp1 and dpp1 lpp1 mutants grow normally. Membership of the pathway is inferred from in vitro substrate range only. Supporting Evidence: PMID:24196957 showed the essential role of PAH1 in triacylglycerol synthesis throughout growth PMID:24196957 are integral membrane enzymes that are localized to the vacuole and Golgi compartments, respectively |
| GO:0046839 phospholipid dephosphorylation | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for phospholipid dephosphorylation at the LPP family node. Directly describes Lpp1's PA/LPA/DGPP phosphatase activity. Supporting Evidence: PMID:10685032 The product of the LPP1 gene in Saccharomyces cerevisiae is a membrane-associated enzyme that catalyzes the Mg(2+)-independent dephosphorylation of phosphatidate (PA), diacylglycerol pyrophosphate (DGPP), and lysophosphatidate (LPA). |
| GO:0052642 lysophosphatidic acid phosphatase activity | EXP PMID:10685032 Enzymological properties of the LPP1-encoded lipid phosphata... | ACCEPT | Summary: SGD EXP from Furneisen and Carman 2000; Lpp1 dephosphorylates LPA (Km 0.08 mol%). Supporting Evidence: PMID:10685032 The LPP1-encoded enzyme exhibited saturation kinetics with respect to the surface concentrations of PA (K(m)=0.05 mol%), DGPP (K(m)=0.07 mol%), and LPA (K(m)=0.08 mol%). |
| GO:0052642 lysophosphatidic acid phosphatase activity | EXP PMID:9603941 Isolation and characterization of the Saccharomyces cerevisi... | ACCEPT | Summary: SGD EXP from Toke et al. 1998; the LPP1 product has lyso-PA phosphatase activity, and Lpp1 plus Dpp1 account for nearly all cellular Mg2+-independent LPA phosphatase. Supporting Evidence: PMID:9603941 The LPP1 gene product also exhibited lyso-PA phosphatase and DGPP phosphatase activities. PMID:9603941 the LPP1 and DPP1 gene products encoded nearly all of the Mg2+-independent PA phosphatase and lyso-PA phosphatase activities and all of the DGPP phosphatase activity in S. cerevisiae |
| GO:0052642 lysophosphatidic acid phosphatase activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA from RHEA/EC 3.1.3.106 mapping derived from UniProt's LPA phosphatase reaction. Correct. Supporting Evidence: file:yeast/LPP1/LPP1-uniprot.txt Reaction=a 1-acyl-sn-glycero-3-phosphate + H2O = a 1-acyl-sn-glycerol + |
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Download this section (compressed HTML)Q: What do Lpp1-generated diacylglycerol or reduced PA do at the Golgi (for example in secretory vesicle formation), given that lpp1 mutants show no obvious growth phenotype?
Q: Which isoprenoid phosphates (dolichyl-P-P, farnesyl-P-P) are physiological Lpp1 substrates in vivo, compared with the dominant Dpp1 activity?
Experiment: Measure Golgi PA/DAG pools (biosensors such as Spo20-PABD and C1 domains) in lpp1, dpp1 and pah1 combinations, with and without catalytically dead Lpp1 (His-189/His-235 mutants).
Hypothesis: Lpp1 sets Golgi PA/DAG levels independently of the Pah1-dependent pool for TAG synthesis.
Type: cell biology/genetics
Lipid phosphate phosphatase; catalyzes Mg(2+)-independent dephosphorylation of phosphatidic acid (PA), lysophosphatidic acid, and diacylglycerol pyrophosphate; involved in control of the cellular levels of phosphatidylinositol and PA
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