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Gene Review

SAC1  -  phosphatidylinositol-3-phosphatase SAC1

Saccharomyces cerevisiae S288c

Synonyms: Phosphoinositide phosphatase SAC1, RSD1, Recessive suppressor of secretory defect, YKL212W
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Disease relevance of SAC1


High impact information on SAC1

  • Here we show that defects in Sac1p also relieve the requirement for Sec14p by altering phospholipid metabolism so as to expand the pool of diacylglycerol (DAG) in the Golgi [3].
  • Here, we show that a COOH-terminal region in yeast Sac1p is crucial for ER targeting by directly interacting with dolicholphosphate mannose synthase Dpm1p [4].
  • The integral membrane lipid phosphatase Sac1p regulates local pools of phosphatidylinositol-4-phosphate (PtdIns(4)P) at endoplasmic reticulum (ER) and Golgi membranes [4].
  • The interaction with Dpm1p persists during exponential cell division but is rapidly abolished when cell growth slows because of nutrient limitation, causing translocation of Sac1p to Golgi membranes [4].
  • Cell growth-dependent shuttling of Sac1p between the ER and the Golgi is important for reciprocal control of PtdIns(4)P levels at these organelles [4].

Biological context of SAC1


Anatomical context of SAC1


Associations of SAC1 with chemical compounds

  • 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 (SEC14p), a protein whose function is essential for sustained Golgi secretory function [11].
  • The fact that Arabidopsis and yeast SAC1 genes derived from a common ancestor suggests that this plant multigenic family is involved in the phosphoinositide pathway and in a range of cellular functions similar to those in yeast [6].
  • We show here that the regulation of lipid phosphoinositides in sac1 mutants is defective, resulting in altered levels of all lipid phos- phoinositides, particularly phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate [7].
  • Preliminary results suggested that deletion of the SAC1 gene eliminated nigericin-stimulated ATP efflux [12].
  • The complete sequencing of a 24.6 kb segment of yeast chromosome XI identified the known loci URA1, SAC1 and TRP3, and revealed 6 new open reading frames including homologues to the threonine dehydratases, membrane transporters, hydantoinases and the phospholipase A2-activating protein [13].

Regulatory relationships of SAC1


Other interactions of SAC1

  • Three of the genes (SAC1, SAC2 and SAC3) were subjected to extensive genetic and phenotypic analysis, including molecular cloning [16].
  • Deletion of SAC1, a gene implicated in vesicular transport, in association with MBR1 deletion, causes synthetic lethality [17].
  • 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 capable of suppressing sec14 lethalities associated with yeast Golgi defects [14].
  • Here we report that SAC1-like domains have intrinsic enzymatic activity that defines a new class of polyphosphoinositide phosphatase (PPIPase) [9].
  • Purified recombinant Inp52p lacking the Sac1 domain hydrolyzed phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)] and PtdIns(3, 5)P(2) [18].

Analytical, diagnostic and therapeutic context of SAC1

  • The yeast Saccharomyces cerevisiae Hsp12 gene was cloned into the Sac1 of the pCAMBIAUbeeQ vector and callus was transformed by biolistic bombardment [19].


  1. Loss of the homotypic fusion and vacuole protein sorting or golgi-associated retrograde protein vesicle tethering complexes results in gentamicin sensitivity in the yeast Saccharomyces cerevisiae. Wagner, M.C., Molnar, E.E., Molitoris, B.A., Goebl, M.G. Antimicrob. Agents Chemother. (2006) [Pubmed]
  2. A domain of human immunodeficiency virus type 1 Vpr containing repeated H(S/F)RIG amino acid motifs causes cell growth arrest and structural defects. Macreadie, I.G., Castelli, L.A., Hewish, D.R., Kirkpatrick, A., Ward, A.C., Azad, A.A. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  3. Essential role for diacylglycerol in protein transport from the yeast Golgi complex. Kearns, B.G., McGee, T.P., Mayinger, P., Gedvilaite, A., Phillips, S.E., Kagiwada, S., Bankaitis, V.A. Nature (1997) [Pubmed]
  4. Cell growth-dependent coordination of lipid signaling and glycosylation is mediated by interactions between Sac1p and Dpm1p. Faulhammer, F., Konrad, G., Brankatschk, B., Tahirovic, S., Knödler, A., Mayinger, P. J. Cell Biol. (2005) [Pubmed]
  5. INP51, a yeast inositol polyphosphate 5-phosphatase required for phosphatidylinositol 4,5-bisphosphate homeostasis and whose absence confers a cold-resistant phenotype. Stolz, L.E., Kuo, W.J., Longchamps, J., Sekhon, M.K., York, J.D. J. Biol. Chem. (1998) [Pubmed]
  6. Three SAC1-like genes show overlapping patterns of expression in Arabidopsis but are remarkably silent during embryo development. Despres, B., Bouissonnié, F., Wu, H.J., Gomord, V., Guilleminot, J., Grellet, F., Berger, F., Delseny, M., Devic, M. Plant J. (2003) [Pubmed]
  7. SAC1 encodes a regulated lipid phosphoinositide phosphatase, defects in which can be suppressed by the homologous Inp52p and Inp53p phosphatases. Hughes, W.E., Woscholski, R., Cooke, F.T., Patrick, R.S., Dove, S.K., McDonald, N.Q., Parker, P.J. J. Biol. Chem. (2000) [Pubmed]
  8. Role for lipid signaling and the cell integrity MAP kinase cascade in yeast septum biogenesis. Tahirovic, S., Schorr, M., Then, A., Berger, J., Schwarz, H., Mayinger, P. Curr. Genet. (2003) [Pubmed]
  9. SAC1-like domains of yeast SAC1, INP52, and INP53 and of human synaptojanin encode polyphosphoinositide phosphatases. Guo, S., Stolz, L.E., Lemrow, S.M., York, J.D. J. Biol. Chem. (1999) [Pubmed]
  10. Regulation of intracellular phosphatidylinositol-4-phosphate by the Sac1 lipid phosphatase. Tahirovic, S., Schorr, M., Mayinger, P. Traffic (2005) [Pubmed]
  11. SAC1p is an integral membrane protein that influences the cellular requirement for phospholipid transfer protein function and inositol in yeast. Whitters, E.A., Cleves, A.E., McGee, T.P., Skinner, H.B., Bankaitis, V.A. J. Cell Biol. (1993) [Pubmed]
  12. Sac1p of Saccharomyces cerevisiae is not involved in ATP release to the extracellular fluid. Boyum, R., Guidotti, G. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  13. The complete sequencing of a 24.6 kb segment of yeast chromosome XI identified the known loci URA1, SAC1 and TRP3, and revealed 6 new open reading frames including homologues to the threonine dehydratases, membrane transporters, hydantoinases and the phospholipase A2-activating protein. Tzermia, M., Horaitis, O., Alexandraki, D. Yeast (1994) [Pubmed]
  14. Mutations in the SAC1 gene suppress defects in yeast Golgi and yeast actin function. Cleves, A.E., Novick, P.J., Bankaitis, V.A. J. Cell Biol. (1989) [Pubmed]
  15. The phosphoinositide phosphatase Sac1p controls trafficking of the yeast Chs3p chitin synthase. Schorr, M., Then, A., Tahirovic, S., Hug, N., Mayinger, P. Curr. Biol. (2001) [Pubmed]
  16. Suppressors of yeast actin mutations. Novick, P., Osmond, B.C., Botstein, D. Genetics (1989) [Pubmed]
  17. The MBR1 gene from Saccharomyces cerevisiae is activated by and required for growth under sub-optimal conditions. Reisdorf, P., Boy-Marcotte, E., Bolotin-Fukuhara, M. Mol. Gen. Genet. (1997) [Pubmed]
  18. The yeast inositol polyphosphate 5-phosphatases inp52p and inp53p translocate to actin patches following hyperosmotic stress: mechanism for regulating phosphatidylinositol 4,5-bisphosphate at plasma membrane invaginations. Ooms, L.M., McColl, B.K., Wiradjaja, F., Wijayaratnam, A.P., Gleeson, P., Gething, M.J., Sambrook, J., Mitchell, C.A. Mol. Cell. Biol. (2000) [Pubmed]
  19. Development of plant regeneration and transformation protocols for the desiccation-sensitive weeping lovegrass Eragrostis curvula. Ncanana, S., Brandt, W., Lindsey, G., Farrant, J. Plant Cell Rep. (2005) [Pubmed]
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