Gene Symbol: SAC1
Description: phosphatidylinositol-3-phosphatase SAC1
Alias: RSD1, phosphatidylinositol-3-phosphatase SAC1
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Cleves A, Novick P, Bankaitis V. Mutations in the SAC1 gene suppress defects in yeast Golgi and yeast actin function. J Cell Biol. 1989;109:2939-50 pubmed
    ..We report here our demonstration that mutations in SAC1, a gene identified by virtue of its allele-specific genetic interactions with yeast actin defects, were also ..
  2. Brice S, Alford C, Cowart L. Modulation of sphingolipid metabolism by the phosphatidylinositol-4-phosphate phosphatase Sac1p through regulation of phosphatidylinositol in Saccharomyces cerevisiae. J Biol Chem. 2009;284:7588-96 pubmed publisher
    ..The data presented indicate that deletion of SAC1, a gene encoding a PtdIns(4)P phosphatase, increased levels of most sphingolipid species, including sphingoid bases,..
  3. Faulhammer F, Konrad G, Brankatschk B, Tahirovic S, Knödler A, Mayinger P. Cell growth-dependent coordination of lipid signaling and glycosylation is mediated by interactions between Sac1p and Dpm1p. J Cell Biol. 2005;168:185-91 pubmed
    ..Thus, the lipid phosphatase Sac1p may be a key regulator, coordinating the secretory capacity of ER and Golgi membranes in response to growth conditions. ..
  4. Tahirovic S, Schorr M, Then A, Berger J, Schwarz H, Mayinger P. Role for lipid signaling and the cell integrity MAP kinase cascade in yeast septum biogenesis. Curr Genet. 2003;43:71-8 pubmed
    ..The phosphoinositide phosphatase Sac1p is required for proper trafficking of the Chs3p chitin synthase. sac1 mutants also display a severe synthetic growth defect, with mutations in the SLT2 gene which encodes a MAP kinase ..
  5. Faulhammer F, Kanjilal Kolar S, Knödler A, Lo J, Lee Y, Konrad G, et al. Growth control of Golgi phosphoinositides by reciprocal localization of sac1 lipid phosphatase and pik1 4-kinase. Traffic. 2007;8:1554-67 pubmed
    Compartment-specific control of phosphoinositide lipids is essential for cell function. The Sac1 lipid phosphatase regulates endoplasmic reticulum (ER) and Golgi phosphatidylinositol-4-phosphate [PI(4)P] in response to nutrient levels and ..
  6. Breslow D, Collins S, Bodenmiller B, Aebersold R, Simons K, Shevchenko A, et al. Orm family proteins mediate sphingolipid homeostasis. Nature. 2010;463:1048-53 pubmed publisher
    ..Our work identifies the Orm proteins as critical mediators of sphingolipid homeostasis and raises the possibility that sphingolipid misregulation contributes to the development of childhood asthma. ..
  7. Tahirovic S, Schorr M, Mayinger P. Regulation of intracellular phosphatidylinositol-4-phosphate by the Sac1 lipid phosphatase. Traffic. 2005;6:116-30 pubmed
    ..Disruption of the SAC1 gene also caused a defect in the late endocytic pathway...
  8. Foti M, Audhya A, Emr S. Sac1 lipid phosphatase and Stt4 phosphatidylinositol 4-kinase regulate a pool of phosphatidylinositol 4-phosphate that functions in the control of the actin cytoskeleton and vacuole morphology. Mol Biol Cell. 2001;12:2396-411 pubmed
    ..By generating double mutant strains harboring the sac1(ts) allele and one of two temperature-sensitive PtdIns 4-kinase genes, stt4(ts) or pik1(ts), we have demonstrated ..
  9. Schorr M, Then A, Tahirovic S, Hug N, Mayinger P. The phosphoinositide phosphatase Sac1p controls trafficking of the yeast Chs3p chitin synthase. Curr Biol. 2001;11:1421-6 pubmed
    ..Members of a subfamily of these enzymes share a specific domain that was first identified in the yeast Sac1 protein [1]...

More Information


  1. Stefan C, Manford A, Baird D, Yamada Hanff J, Mao Y, Emr S. Osh proteins regulate phosphoinositide metabolism at ER-plasma membrane contact sites. Cell. 2011;144:389-401 pubmed publisher
    b>Sac1 phosphoinositide (PI) phosphatases are essential regulators of PI-signaling networks. Yeast Sac1, an integral endoplasmic reticulum (ER) membrane protein, controls PI4P levels at the ER, Golgi, and plasma membrane (PM)...
  2. Konrad G, Schlecker T, Faulhammer F, Mayinger P. Retention of the yeast Sac1p phosphatase in the endoplasmic reticulum causes distinct changes in cellular phosphoinositide levels and stimulates microsomal ATP transport. J Biol Chem. 2002;277:10547-54 pubmed
    ..ER also stimulates ATP transport into the ER lumen but causes the same Golgi-specific defects that are seen in a sac1 null mutant...
  3. Hama H, Schnieders E, Thorner J, Takemoto J, DeWald D. Direct involvement of phosphatidylinositol 4-phosphate in secretion in the yeast Saccharomyces cerevisiae. J Biol Chem. 1999;274:34294-300 pubmed
    ..One suppressor, sac1-22, causes accumulation of PtdIns(4)P...
  4. Wood C, Hung C, Huoh Y, Mousley C, Stefan C, BANKAITIS V, et al. Local control of phosphatidylinositol 4-phosphate signaling in the Golgi apparatus by Vps74 and Sac1 phosphoinositide phosphatase. Mol Biol Cell. 2012;23:2527-36 pubmed publisher
    ..Vps74 binds directly to the catalytic domain of Sac1 (K(D) = 3...
  5. Kearns B, McGee T, Mayinger P, Gedvilaite A, Phillips S, Kagiwada S, et al. Essential role for diacylglycerol in protein transport from the yeast Golgi complex. Nature. 1997;387:101-5 pubmed
    ..The essential function of Sec14p may therefore be to maintain a sufficient pool of DAG in the Golgi to support the production of secretory vesicles. ..
  6. Whitters E, Cleves A, McGee T, Skinner H, Bankaitis V. SAC1p is an integral membrane protein that influences the cellular requirement for phospholipid transfer protein function and inositol in yeast. J Cell Biol. 1993;122:79-94 pubmed
    Mutations in the SAC1 gene exhibit allele-specific genetic interactions with yeast actin structural gene defects and effect a bypass of the cellular requirement for the yeast phosphatidylinositol/phosphatidylcholine transfer protein (..
  7. Ha S, Torabinejad J, DeWald D, Wenk M, Lucast L, De Camilli P, et al. The synaptojanin-like protein Inp53/Sjl3 functions with clathrin in a yeast TGN-to-endosome pathway distinct from the GGA protein-dependent pathway. Mol Biol Cell. 2003;14:1319-33 pubmed
    ..Taken together with other recent studies, our results suggest that Inp53p and AP-1/clathrin act together in a TGN-to-early endosome pathway distinct from the direct TGN-to-PVC pathway mediated by GGA/clathrin. ..
  8. Knödler A, Konrad G, Mayinger P. Expression of yeast lipid phosphatase Sac1p is regulated by phosphatidylinositol-4-phosphate. BMC Mol Biol. 2008;9:16 pubmed publisher
    ..Unlike genes encoding enzymes involved in phospholipid biosynthesis, expression of the SAC1 gene is independent of inositol levels...
  9. Baird D, Stefan C, Audhya A, Weys S, Emr S. Assembly of the PtdIns 4-kinase Stt4 complex at the plasma membrane requires Ypp1 and Efr3. J Cell Biol. 2008;183:1061-74 pubmed publisher
    ..Efr3 is essential for assembly of both Ypp1 and Stt4 at PIK patches. We conclude that Ypp1 and Efr3 are required for the formation and architecture of Stt4 PIK patches and ultimately PM-based PtdIns4P signaling. ..
  10. Alfaro G, Johansen J, Dighe S, Duamel G, Kozminski K, Beh C. The sterol-binding protein Kes1/Osh4p is a regulator of polarized exocytosis. Traffic. 2011;12:1521-36 pubmed publisher
    ..These results support a model in which Osh4p acts as a sterol-dependent regulator of polarized vesicle transport, as opposed to being a sterol-transfer protein. ..
  11. Moser von Filseck J, Čopič A, Delfosse V, Vanni S, Jackson C, Bourguet W, et al. INTRACELLULAR TRANSPORT. Phosphatidylserine transport by ORP/Osh proteins is driven by phosphatidylinositol 4-phosphate. Science. 2015;349:432-6 pubmed publisher
    ..Thus, PS transport by oxysterol-binding protein-related protein (ORP)/oxysterol-binding homology (Osh) proteins is fueled by PI4P metabolism through PS/PI4P exchange cycles. ..
  12. Yakir Tamang L, Gerst J. A phosphatidylinositol-transfer protein and phosphatidylinositol-4-phosphate 5-kinase control Cdc42 to regulate the actin cytoskeleton and secretory pathway in yeast. Mol Biol Cell. 2009;20:3583-97 pubmed publisher
    ..Based upon these findings, we propose that the exocytic signal involves PI delivery to the PI kinases (i.e., Mss4) by Sfh5, generation of PI(4,5)P(2), and PI(4,5)P(2)-dependent regulation of Cdc42 and the actin cytoskeleton. ..
  13. Puts C, Lenoir G, Krijgsveld J, Williamson P, Holthuis J. A P4-ATPase protein interaction network reveals a link between aminophospholipid transport and phosphoinositide metabolism. J Proteome Res. 2010;9:833-42 pubmed publisher
    ..Together, these findings suggest that aminophospholipid transport and phosphoinositide metabolism are interconnected at the Golgi. ..
  14. Wiradjaja F, Ooms L, Tahirovic S, Kuhne E, Devenish R, Munn A, et al. Inactivation of the phosphoinositide phosphatases Sac1p and Inp54p leads to accumulation of phosphatidylinositol 4,5-bisphosphate on vacuole membranes and vacuolar fusion defects. J Biol Chem. 2007;282:16295-307 pubmed
  15. James A, Cocheme H, Murai M, Miyoshi H, Murphy M. Complementation of coenzyme Q-deficient yeast by coenzyme Q analogues requires the isoprenoid side chain. FEBS J. 2010;277:2067-82 pubmed publisher
    ..Here we suggest that CoQ or its redox state may be a signal for growth during the shift to respiration. ..
  16. Santiago Tirado F, Legesse Miller A, Schott D, Bretscher A. PI4P and Rab inputs collaborate in myosin-V-dependent transport of secretory compartments in yeast. Dev Cell. 2011;20:47-59 pubmed publisher
    ..Thus, we show that a coincidence detection mechanism coordinates inputs from PI4P and the appropriate Rab for secretory compartment transport. ..
  17. Li X, Rivas M, Fang M, Marchena J, Mehrotra B, Chaudhary A, et al. Analysis of oxysterol binding protein homologue Kes1p function in regulation of Sec14p-dependent protein transport from the yeast Golgi complex. J Cell Biol. 2002;157:63-77 pubmed
  18. Cai Y, Deng Y, Horenkamp F, Reinisch K, Burd C. Sac1-Vps74 structure reveals a mechanism to terminate phosphoinositide signaling in the Golgi apparatus. J Cell Biol. 2014;206:485-91 pubmed publisher
    b>Sac1 is a phosphoinositide phosphatase of the endoplasmic reticulum and Golgi apparatus that controls organelle membrane composition principally via regulation of phosphatidylinositol 4-phosphate signaling...
  19. Reisdorf P, Boy Marcotte E, Bolotin Fukuhara M. The MBR1 gene from Saccharomyces cerevisiae is activated by and required for growth under sub-optimal conditions. Mol Gen Genet. 1997;255:400-9 pubmed
    ..Our results indicate that Mbr1p is not an essential element of any one of these pathways. Deletion of SAC1, a gene implicated in vesicular transport, in association with MBR1 deletion, causes synthetic lethality...
  20. Novick P, Osmond B, Botstein D. Suppressors of yeast actin mutations. Genetics. 1989;121:659-74 pubmed
    ..Three of the genes (SAC1, SAC2 and SAC3) were subjected to extensive genetic and phenotypic analysis, including molecular cloning...
  21. Zhai C, Li K, Markaki V, Phelan J, Bowers K, Cooke F, et al. Ypp1/YGR198w plays an essential role in phosphoinositide signalling at the plasma membrane. Biochem J. 2008;415:455-66 pubmed publisher
    ..the principal cause of lethality under non-permissive conditions in ypp1 mutants, as limiting the activity of the Sac1 phosphoinositide 4-phosphate phosphatase leads to restoration of viability...
  22. Morimoto Y, Tani M. Synthesis of mannosylinositol phosphorylceramides is involved in maintenance of cell integrity of yeast Saccharomyces cerevisiae. Mol Microbiol. 2015;95:706-22 pubmed publisher
    ..These results indicated that loss of MIPC synthesis causes impairment of cell integrity, and this effect is enhanced by impaired synthesis of mannan-type N-glycans. ..
  23. Tani M, Kuge O. Involvement of Sac1 phosphoinositide phosphatase in the metabolism of phosphatidylserine in the yeast Saccharomyces cerevisiae. Yeast. 2014;31:145-58 pubmed publisher
    b>Sac1 is a phosphoinositide phosphatase that preferentially dephosphorylates phosphatidylinositol 4-phosphate...
  24. Shimobayashi M, Oppliger W, Moes S, Jeno P, Hall M. TORC1-regulated protein kinase Npr1 phosphorylates Orm to stimulate complex sphingolipid synthesis. Mol Biol Cell. 2013;24:870-81 pubmed publisher
    ..Thus activation of Orm and complex sphingolipid synthesis upon TORC1 inhibition is a physiological response to starvation. ..
  25. Piao H, Maclean Freed J, Mayinger P. Metabolic activation of the HOG MAP kinase pathway by Snf1/AMPK regulates lipid signaling at the Golgi. Traffic. 2012;13:1522-31 pubmed publisher
    ..Metabolic regulation of Golgi PI(4)P requires the lipid phosphatase Sac1 that translocates between endoplasmic reticulum (ER) and Golgi membranes...
  26. Zhong S, Hsu F, Stefan C, Wu X, Patel A, Cosgrove M, et al. Allosteric activation of the phosphoinositide phosphatase Sac1 by anionic phospholipids. Biochemistry. 2012;51:3170-7 pubmed publisher
    ..Our recently determined crystal structure of the Sac phosphatase domain of yeast Sac1, the founding member of the Sac family proteins, revealed a unique conformation of the catalytic P-loop and a large ..
  27. Hughes W, Woscholski R, Cooke F, Patrick R, Dove S, McDonald N, et al. SAC1 encodes a regulated lipid phosphoinositide phosphatase, defects in which can be suppressed by the homologous Inp52p and Inp53p phosphatases. J Biol Chem. 2000;275:801-8 pubmed
    ..We show here that the regulation of lipid phosphoinositides in sac1 mutants is defective, resulting in altered levels of all lipid phos- phoinositides, particularly ..
  28. Tani M, Kuge O. Requirement of a specific group of sphingolipid-metabolizing enzyme for growth of yeast Saccharomyces cerevisiae under impaired metabolism of glycerophospholipids. Mol Microbiol. 2010;78:395-413 pubmed
    ..high sensitivity to Aureobasidin A, an inhibitor of inositol phosphorylceramide synthase, and found that a lack of SAC1 encoding phosphoinositides phosphatase causes high sensitivity to the inhibitor...