PAH1 (formerly SMP2) encodes the yeast lipin, the Mg2+-dependent phosphatidate phosphatase (PAP1; EC 3.1.3.4). It dephosphorylates phosphatidic acid (PA) to diacylglycerol (DAG) using a haloacid dehalogenase-like DXDX(T/V) catalytic motif (DIDGT, Asp-398/Asp-400). Pah1 controls whether PA is used for membrane phospholipid synthesis via CDP-diacylglycerol or for DAG and hence triacylglycerol (TAG) and Kennedy-pathway phospholipids. Among the four yeast PA phosphatases (Pah1, App1, Dpp1, Lpp1), Pah1 is the one essential for TAG synthesis throughout growth. Pah1 is a soluble protein, phosphorylated in the cytosol by several kinases (Cdc28, Pho85, PKA, PKC, Hsl1 and others), which keeps it inactive. Dephosphorylation by the Nem1-Spo7 phosphatase at the nuclear/ER membrane lets its N-terminal amphipathic helix anchor it to the membrane, where it is active. Loss of Pah1 raises PA, derepresses phospholipid genes through the PA-Opi1-Ino2/Ino4 circuit and causes nuclear/ER membrane expansion. The pah1 mutant also has fewer lipid droplets, fragmented vacuoles defective in homotypic fusion, respiratory deficiency and temperature sensitivity, all of which depend on loss of PAP activity.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000976 transcription cis-regulatory region binding | IDA PMID:15889145 The yeast lipin Smp2 couples phospholipid biosynthesis to nu... | MARK AS OVER ANNOTATED | Summary: IDA from Santos-Rosa et al. 2005, based on chromatin immunoprecipitation showing Smp2/Pah1 associated with promoters of phospholipid biosynthetic genes in a Nem1-Spo7-dependent manner. Reason: Association with promoter chromatin by ChIP does not show sequence-specific or direct DNA binding, and Pah1 has no DNA-binding domain. Its effect on phospholipid gene expression is explained by its control of PA levels through the Opi1-Ino2/Ino4 circuit. The experimental association is not disputed, but a cis-regulatory DNA-binding activity overstates it. Supporting Evidence: PMID:15889145 We show that Smp2 associates with the promoters of phospholipid biosynthetic enzymes in a Nem1-Spo7-dependent manner. PMID:17971454 failed to complement the pah1Delta mutant phenotypes of temperature sensitivity, respiratory deficiency, nuclear/endoplasmic reticulum membrane expansion, derepression of INO1 expression, and alterations in lipid composition |
| GO:0005634 nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT IBA (is_active_in nucleus) at the lipin node, grounded in fly, mouse, worm and yeast lipins. Reason: Pah1 acts at the nuclear envelope and has been found at promoter chromatin. Its catalytic role, however, is at the cytoplasmic face of the nuclear/ER membrane. Nuclear localisation is non-core for yeast Pah1. Supporting Evidence: PMID:15889145 We show that Smp2 associates with the promoters of phospholipid biosynthetic enzymes in a Nem1-Spo7-dependent manner. PMID:39009344 activated via its recruitment and dephosphorylation by the protein phosphatase Nem1-Spo7 at the nuclear/endoplasmic reticulum membrane where the PA phosphatase reaction occurs |
| GO:0005737 cytoplasm | HDA PMID:14562095 Global analysis of protein localization in budding yeast. | ACCEPT | Summary: HDA from the Huh et al. 2003 GFP survey (cytoplasm). Pah1 is largely cytosolic when phosphorylated. Supporting Evidence: PMID:14562095 expressing full-length, chromosomally tagged green fluorescent protein fusion proteins PMID:35026226 Pah1 is inactive in the cytosol as a phosphorylated form and becomes active on the membrane as a dephosphorylated form by the Nem1-Spo7 protein phosphatase. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from UniProt subcellular location (SL-0086 cytoplasm). Correct. Supporting Evidence: file:yeast/PAH1/PAH1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. Nucleus membrane; Peripheral membrane |
| GO:0005773 vacuole | IDA PMID:22121197 Yeast lipin 1 orthologue pah1p regulates vacuole homeostasis... | KEEP AS NON CORE | Summary: IDA from Sasser et al. 2012; Pah1-GFP was recruited to the vacuolar membrane, and pah1 vacuoles are fragmented and fusion-defective. Reason: Vacuolar association is real but minor relative to the nuclear/ER membrane, where Pah1 does its main PAP work. Supporting Evidence: PMID:22121197 This further demonstrated that Pah1p-GFP was truly recruited to the vacuolar membrane and not associated with contaminating membranes. |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from UniProt subcellular location (SL-0097 ER membrane, peripheral). Correct; dephosphorylated Pah1 binds the nuclear/ER membrane through its amphipathic helix. Supporting Evidence: PMID:20876142 Once dephosphorylated, Pah1p can bind to the nuclear/ER membrane independently of Nem1p-Spo7p via a short amino-terminal amphipathic helix. |
| GO:0005811 lipid droplet | IDA PMID:26275961 Seipin is involved in the regulation of phosphatidic acid me... | KEEP AS NON CORE | Summary: IDA from Wolinski et al. 2015; Pah1 and Nem1 are highly enriched at a nuclear envelope subdomain tightly associated with clustered lipid droplets in seipin (fld1/ldb16) mutants. Reason: The cached abstract describes enrichment at an LD-associated nuclear envelope subdomain rather than on the droplet surface. The curator saw the full text, so the row is kept, but as non-core. Supporting Evidence: PMID:26275961 The human lipin-1 ortholog, the PAH1 encoded phosphatidic acid (PA) phosphatase, and its activator Nem1 are highly enriched at this site. |
| GO:0005829 cytosol | HDA PMID:26928762 One library to make them all: streamlining the creation of y... | ACCEPT | Summary: HDA from the SWAT GFP library (Yofe et al. 2016) scoring Pah1 as cytosolic. Supporting Evidence: PMID:26928762 carrying SWAT-GFP modules at the amino termini of endomembrane proteins PMID:35026226 Pah1 is inactive in the cytosol as a phosphorylated form and becomes active on the membrane as a dephosphorylated form by the Nem1-Spo7 protein phosphatase. |
| GO:0005829 cytosol | IDA PMID:16467296 The Saccharomyces cerevisiae Lipin homolog is a Mg2+-depende... | ACCEPT | Summary: IDA from Han et al. 2006; PAH1-encoded PAP activity was found in both cytosolic and membrane fractions. Supporting Evidence: PMID:16467296 The PAH1-encoded enzyme activity was associated with both the membrane and cytosolic fractions of the cell |
| GO:0005829 cytosol | RCA GO_REF:0000123 | MODIFY | Summary: YeastPathways RCA asserting Pah1 is active in the cytosol for the PA -> DAG step of TRIGLSYN-PWY. Reason: Pah1 is located in the cytosol, but it is inactive there as a phosphoprotein. The PA phosphatase reaction takes place after Nem1-Spo7 recruits it to the nuclear/ER membrane. For the activity location, the ER membrane (or nuclear membrane) is the correct term; cytosol is right only as a located_in statement, which the HDA/IDA rows already cover. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: PMID:35026226 Pah1 is inactive in the cytosol as a phosphorylated form and becomes active on the membrane as a dephosphorylated form by the Nem1-Spo7 protein phosphatase. PMID:39009344 activated via its recruitment and dephosphorylation by the protein phosphatase Nem1-Spo7 at the nuclear/endoplasmic reticulum membrane where the PA phosphatase reaction occurs |
| GO:0006276 plasmid maintenance | IMP PMID:8437575 A gene, SMP2, involved in plasmid maintenance and respiratio... | KEEP AS NON CORE | Summary: IMP from Irie et al. 1993; the smp2 mutant shows increased stability of pSR1 and YRp plasmids. Reason: This is a pleiotropic phenotype from the original SMP2 screen. No mechanism links PAP activity to plasmid maintenance, so it is kept as non-core. Supporting Evidence: PMID:8437575 The smp2 mutant of Saccharomyces cerevisiae shows increased stability of the heterologous plasmid pSR1 and YRp plasmids. |
| GO:0006651 diacylglycerol biosynthetic process | IDA PMID:39009344 Protein kinase Hsl1 phosphorylates Pah1 to inhibit phosphati... | ACCEPT | Summary: IDA from Khondker et al. 2024; Pah1 dephosphorylates PA to DAG, and the Hsl1-phosphorylated form has 5-fold lower catalytic efficiency. Supporting Evidence: PMID:39009344 Pah1 plays a key role in the use of PA for the synthesis of membrane phospholipids via CDP-DAG or the synthesis of TAG via DAG. PMID:39009344 the phosphorylated protein exhibited a 5-fold reduction in PA phosphatase catalytic efficiency |
| GO:0008195 phosphatidate phosphatase activity | EXP PMID:17910939 Colorimetric determination of pure Mg(2+)-dependent phosphat... | ACCEPT | Summary: SGD EXP from Havriluk et al. 2008; colorimetric assay of pure Mg2+-dependent PAP (Pah1). Supporting Evidence: PMID:17910939 The malachite green-molybdate reagent was used for a colorimetric assay of pure Mg2(+)-dependent phosphatidate phosphatase activity. |
| GO:0008195 phosphatidate phosphatase activity | EXP PMID:17971454 The cellular functions of the yeast lipin homolog PAH1p are ... | ACCEPT | Summary: SGD EXP from Han et al. 2007; mutating the DXDXT catalytic Asp residues abolished PAP1 activity. Supporting Evidence: PMID:17971454 The PAP1 activities of the D398E and D400E mutant enzymes were reduced by >99.9% |
| GO:0008195 phosphatidate phosphatase activity | EXP PMID:39577771 The antidepressant drug sertraline is a novel inhibitor of y... | ACCEPT | Summary: SGD EXP from Stukey et al. 2024; Pah1 PAP activity is inhibited noncompetitively by sertraline. Supporting Evidence: PMID:39577771 Using Saccharomyces cerevisiae Pah1 as a model PAP, sertraline inhibited the activity by a noncompetitive mechanism. |
| GO:0008195 phosphatidate phosphatase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for phosphatidate phosphatase activity at the lipin node (yeast Pah1, fly, mouse and human lipins). Correct. Supporting Evidence: file:yeast/PAH1/PAH1-uniprot.txt SIMILARITY: Belongs to the lipin family. PMID:16467296 Heterologous expression of PAH1 in Escherichia coli confirmed that Pah1p is a Mg(2+)-dependent PA phosphatase enzyme |
| GO:0008195 phosphatidate phosphatase activity | IDA PMID:16467296 The Saccharomyces cerevisiae Lipin homolog is a Mg2+-depende... | ACCEPT | Summary: IDA from Han et al. 2006 (gene identification); Pah1 expressed in E. coli is a Mg2+-dependent PA phosphatase. Supporting Evidence: PMID:16467296 Heterologous expression of PAH1 in Escherichia coli confirmed that Pah1p is a Mg(2+)-dependent PA phosphatase enzyme |
| GO:0008195 phosphatidate phosphatase activity | IDA PMID:29765047 Tip60-mediated lipin 1 acetylation and ER translocation dete... | ACCEPT | Summary: IDA from Li et al. 2018 (Tip60/Esa1 acetylation of lipin); Esa1-mediated acetylation of Pah1 promotes its PAP-dependent TAG synthesis. Supporting Evidence: PMID:29765047 These results reveal that PAH1 acetylation, most likely via the Tip60 ortholog ESA1, plays a conserved role in TAG storage |
| GO:0008195 phosphatidate phosphatase activity | IDA PMID:35026226 Mutant phosphatidate phosphatase Pah1-W637A exhibits altered... | ACCEPT | Summary: IDA from Park et al. 2022; PAP activity measured for wild-type and W637A Pah1. Supporting Evidence: PMID:35026226 Pah1 is inactive in the cytosol as a phosphorylated form and becomes active on the membrane as a dephosphorylated form by the Nem1-Spo7 protein phosphatase. |
| GO:0008195 phosphatidate phosphatase activity | IDA PMID:39009344 Protein kinase Hsl1 phosphorylates Pah1 to inhibit phosphati... | ACCEPT | Summary: IDA from Khondker et al. 2024; PAP activity assays with Hsl1-phosphorylated Pah1. Supporting Evidence: PMID:39009344 the phosphorylated protein exhibited a 5-fold reduction in PA phosphatase catalytic efficiency |
| GO:0008195 phosphatidate phosphatase activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA from RHEA/EC 3.1.3.4 mapping derived from UniProt's PAP reaction. Correct. Supporting Evidence: file:yeast/PAH1/PAH1-uniprot.txt Reaction=a 1,2-diacyl-sn-glycero-3-phosphate + H2O = a 1,2-diacyl-sn- |
| GO:0008195 phosphatidate phosphatase activity | IMP PMID:16467296 The Saccharomyces cerevisiae Lipin homolog is a Mg2+-depende... | ACCEPT | Summary: IMP from Han et al. 2006; pah1 deletion reduced Mg2+-dependent PAP activity. Supporting Evidence: PMID:16467296 Overexpression of PAH1 in S. cerevisiae directed elevated levels of Mg(2+)-dependent PA phosphatase activity, whereas the pah1Delta mutation caused reduced levels of enzyme activity. |
| 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 Pah1. Correct; Pah1 is the PAP that supplies DAG for TAG. Supporting Evidence: PMID:24196957 showed the essential role of PAH1 in triacylglycerol synthesis throughout growth |
| GO:0008654 phospholipid biosynthetic process | IMP PMID:16467296 The Saccharomyces cerevisiae Lipin homolog is a Mg2+-depende... | ACCEPT | Summary: IMP from Han et al. 2006; pah1 mutants accumulate PA and have altered lipid composition. Reason: Pah1-produced DAG feeds the Kennedy pathway for PC/PE synthesis, and its activity controls PA flux into CDP-DAG-derived phospholipids. This is a direct catalytic contribution to phospholipid synthesis. Supporting Evidence: PMID:16467296 Lipid analysis showed that mutants lacking PAH1 accumulated PA and had reduced amounts of diacylglycerol and its derivative triacylglycerol. PMID:39009344 Pah1 plays a key role in the use of PA for the synthesis of membrane phospholipids via CDP-DAG or the synthesis of TAG via DAG. |
| GO:0008654 phospholipid biosynthetic process | IMP PMID:17971454 The cellular functions of the yeast lipin homolog PAH1p are ... | ACCEPT | Summary: IMP from Han et al. 2007; PAP-dead Pah1 alleles fail to restore normal lipid composition. Supporting Evidence: PMID:17971454 This enzyme plays a major role in the synthesis of triacylglycerols and phospholipids in S. cerevisiae. PMID:17971454 failed to complement the pah1Delta mutant phenotypes of temperature sensitivity, respiratory deficiency, nuclear/endoplasmic reticulum membrane expansion, derepression of INO1 expression, and alterations in lipid composition |
| GO:0008654 phospholipid biosynthetic process | IMP PMID:35026226 Mutant phosphatidate phosphatase Pah1-W637A exhibits altered... | ACCEPT | Summary: IMP from Park et al. 2022; Pah1-W637A alters membrane phospholipid synthesis. Supporting Evidence: PMID:35026226 is required for normal synthesis of membrane phospholipids, sterols, triacylglycerol, and the formation of lipid droplets |
| GO:0009060 aerobic respiration | IMP PMID:8437575 A gene, SMP2, involved in plasmid maintenance and respiratio... | KEEP AS NON CORE | Summary: IMP from Irie et al. 1993; smp2 disruption causes a respiration-deficient phenotype although mtDNA is retained. Reason: Pleiotropic consequence of losing PAP activity (Han et al. 2007 show respiratory deficiency depends on PAP activity). Pah1 does not take part in respiration directly; non-core. Supporting Evidence: PMID:8437575 Disruption of the genomic SMP2 gene resulted in a respiration-deficient phenotype, although the cells retained mitochondrial DNA PMID:17971454 failed to complement the pah1Delta mutant phenotypes of temperature sensitivity, respiratory deficiency, nuclear/endoplasmic reticulum membrane expansion, derepression of INO1 expression, and alterations in lipid composition |
| GO:0009062 fatty acid catabolic process | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: PAINT IBA for fatty acid catabolic process from a lipin node grounded in mouse Lpin1 and Dictyostelium. Reason: In mammals this annotation reflects lipin-1's role as a PGC-1alpha/PPARalpha transcriptional coactivator of fatty-acid oxidation genes, which has no counterpart in S. cerevisiae (no PPARs). No evidence links yeast Pah1 to fatty-acid catabolism; its documented roles are PA dephosphorylation for TAG and phospholipid synthesis. Propagation Review Root cause: PROPAGATION BAD Failure modes: LINEAGE OR TAXON MISMATCH Sources checked: MGI:MGI:1891340 · Lpin1 (mouse) SUPPORTS SOURCE BUT NOT TARGET Mouse lipin-1 fatty-acid oxidation role is mediated by PPARalpha/PGC-1alpha coactivation, which has no budding-yeast counterpart. Supporting Evidence: PMID:39009344 Pah1 plays a key role in the use of PA for the synthesis of membrane phospholipids via CDP-DAG or the synthesis of TAG via DAG. |
| GO:0019432 triglyceride biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for triglyceride biosynthetic process at the lipin node. Correct for Pah1. Supporting Evidence: PMID:24196957 showed the essential role of PAH1 in triacylglycerol synthesis throughout growth |
| GO:0019432 triglyceride biosynthetic process | IDA PMID:29765047 Tip60-mediated lipin 1 acetylation and ER translocation dete... | ACCEPT | Summary: IDA from Li et al. 2018; pah1 cells reconstituted with an acetylation-defective Pah1 accumulate much less TAG. Supporting Evidence: PMID:29765047 PAH1 plays an essential role in TAG synthesis throughout growth PMID:29765047 These results reveal that PAH1 acetylation, most likely via the Tip60 ortholog ESA1, plays a conserved role in TAG storage |
| GO:0019432 triglyceride biosynthetic process | IGI PMID:24196957 PAH1-encoded phosphatidate phosphatase plays a role in the g... | ACCEPT | Summary: IGI from Pascual et al. 2013, analysing pah1 in combination with dpp1 and lpp1 (with/from DPP1, LPP1). Among the four PAP genes, PAH1 is the one essential for TAG synthesis throughout growth. Supporting Evidence: PMID:24196957 showed the essential role of PAH1 in triacylglycerol synthesis throughout growth PMID:24196957 Four genes (APP1, DPP1, LPP1, and PAH1) encode PAP activity in yeast |
| GO:0019432 triglyceride biosynthetic process | IGI PMID:24196957 PAH1-encoded phosphatidate phosphatase plays a role in the g... | ACCEPT | Summary: IGI from Pascual et al. 2013, analysing pah1 in combination with dpp1 and lpp1 (with/from DPP1, LPP1). Among the four PAP genes, PAH1 is the one essential for TAG synthesis throughout growth. Supporting Evidence: PMID:24196957 showed the essential role of PAH1 in triacylglycerol synthesis throughout growth PMID:24196957 Four genes (APP1, DPP1, LPP1, and PAH1) encode PAP activity in yeast |
| GO:0019432 triglyceride biosynthetic process | IMP PMID:24196957 PAH1-encoded phosphatidate phosphatase plays a role in the g... | ACCEPT | Summary: IMP from Pascual et al. 2013; pah1 mutants are defective in TAG synthesis in all growth phases. Supporting Evidence: PMID:24196957 showed the essential role of PAH1 in triacylglycerol synthesis throughout growth |
| GO:0019432 triglyceride biosynthetic process | IMP PMID:35026226 Mutant phosphatidate phosphatase Pah1-W637A exhibits altered... | ACCEPT | Summary: IMP from Park et al. 2022; Pah1-W637A affects TAG synthesis. Supporting Evidence: PMID:35026226 is required for normal synthesis of membrane phospholipids, sterols, triacylglycerol, and the formation of lipid droplets |
| GO:0031965 nuclear membrane | IDA PMID:20876142 A phosphorylation-regulated amphipathic helix controls the m... | ACCEPT | Summary: IDA from Karanasios et al. 2010; dephosphorylated Pah1 binds the nuclear/ER membrane via its N-terminal amphipathic helix. Supporting Evidence: PMID:20876142 Once dephosphorylated, Pah1p can bind to the nuclear/ER membrane independently of Nem1p-Spo7p via a short amino-terminal amphipathic helix. |
| GO:0031965 nuclear membrane | IDA PMID:35026226 Mutant phosphatidate phosphatase Pah1-W637A exhibits altered... | ACCEPT | Summary: IDA (is_active_in nuclear membrane) from Park et al. 2022; Pah1 becomes active on the membrane after Nem1-Spo7 dephosphorylation. Supporting Evidence: PMID:35026226 Pah1 is inactive in the cytosol as a phosphorylated form and becomes active on the membrane as a dephosphorylated form by the Nem1-Spo7 protein phosphatase. PMID:39009344 activated via its recruitment and dephosphorylation by the protein phosphatase Nem1-Spo7 at the nuclear/endoplasmic reticulum membrane where the PA phosphatase reaction occurs |
| GO:0031965 nuclear membrane | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from UniProt subcellular location (SL-0182 nucleus membrane). Correct. Supporting Evidence: file:yeast/PAH1/PAH1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. Nucleus membrane; Peripheral membrane |
| GO:0034389 lipid droplet organization | IGI PMID:21829381 A role for phosphatidic acid in the formation of "supersized... | KEEP AS NON CORE | Summary: IGI from Fei et al. 2011 (supersized lipid droplet screen), with two other genes from that screen (with/from SGD ids). PA accumulation promotes droplet coalescence, and PAH1 or DPP1 overexpression suppresses supersized droplets. Reason: Pah1 affects droplet size and number through its control of PA/DAG levels. That is an indirect effect of its PAP activity rather than direct work in droplet organisation; non-core. Supporting Evidence: PMID:21829381 Results from in vivo and in vitro analyses indicate that PA may facilitate the coalescence of contacting LDs PMID:21829381 Overexpression of PAH1 and DPP1 significantly reduces the formation of SLDs |
| GO:0034389 lipid droplet organization | IGI PMID:21829381 A role for phosphatidic acid in the formation of "supersized... | KEEP AS NON CORE | Summary: IGI from Fei et al. 2011 (supersized lipid droplet screen), with two other genes from that screen (with/from SGD ids). PA accumulation promotes droplet coalescence, and PAH1 or DPP1 overexpression suppresses supersized droplets. Reason: Pah1 affects droplet size and number through its control of PA/DAG levels. That is an indirect effect of its PAP activity rather than direct work in droplet organisation; non-core. Supporting Evidence: PMID:21829381 Results from in vivo and in vitro analyses indicate that PA may facilitate the coalescence of contacting LDs PMID:21829381 Overexpression of PAH1 and DPP1 significantly reduces the formation of SLDs |
| GO:0034389 lipid droplet organization | IMP PMID:21422231 The yeast lipin orthologue Pah1p is important for biogenesis... | KEEP AS NON CORE | Summary: IMP from Adeyo et al. 2011; pah1 deletion reduced droplet number by 63%, and DAG made by Pah1 is important for droplet biogenesis. Reason: Pah1 supplies DAG for droplet biogenesis, so it contributes, but the process-specific machinery (seipin, Nem1 sites, TAG synthases) lies elsewhere. Retain as non-core. Supporting Evidence: PMID:21422231 Disruption of PAH1 resulted in a 63% decrease in droplet number, although total neutral lipid levels did not change. PMID:21422231 this study provides strong evidence that DAG generated by Pah1p is important for droplet biogenesis |
| GO:0042144 vacuole fusion, non-autophagic | IMP PMID:22121197 Yeast lipin 1 orthologue pah1p regulates vacuole homeostasis... | KEEP AS NON CORE | Summary: IMP from Sasser et al. 2012; pah1 deletion causes vacuole fragmentation and abolishes homotypic vacuole fusion, and this depends on PAP activity. Reason: Fusion requires DAG and correct PA levels at the vacuole. Pah1's contribution is via lipid supply rather than fusion machinery; non-core. Supporting Evidence: PMID:22121197 Deletion of PAH1 was sufficient to cause marked vacuole fragmentation and abolish vacuole fusion. PMID:22121197 The function of Pah1p solely depended on its phosphatase activity |
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Download this section (compressed HTML)Q: How do the many Pah1 kinases (Cdc28, Pho85, PKA, PKC, CK1/CK2, Hsl1) combine to set the pool of active, membrane-bound Pah1 across growth phases?
Q: Does the reported promoter association of Pah1 have any role beyond its control of PA levels and Opi1 release?
Experiment: ChIP-seq of Pah1 in strains with a catalytically dead Pah1 (D398E) or with Opi1 deleted, to test whether promoter occupancy is direct and independent of PA signalling.
Hypothesis: Pah1 promoter association is an indirect consequence of nuclear-envelope proximity, and gene regulation acts entirely through PA levels.
Type: genomics/genetics
Mg2+-dependent phosphatidate (PA) phosphatase; dephosphorylates PA to yield diacylglycerol; regulates phospholipid synthesis, nuclear/ER membrane growth, lipid droplet formation, triacylglycerol synthesis, vacuolar homeostasis and cell wall integrity; phosphorylated by Hsl1p, Pho85p/Pho80p, Cdc28p/Cyclin B, PKA, PKC, and CKII, regulating activity, localization, and proteosomal degradation; homolog of mammalian lipins 1 and 2; human homologs LPIN1, LPIN2, LPIN3 complement the null
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