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1,2-dihexadecanoyl-sn-glycero-phospho-1-D-myo-inositol 4-phosphate + H2O
1,2-dihexadecanoyl-sn-glycero-phospho-1-D-myo-inositol + phosphate
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phosphatidylinositol 4-phosphate + H2O
phosphatidylinositol + phosphate
additional information
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phosphatidylinositol 4-phosphate + H2O
phosphatidylinositol + phosphate
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phosphatidylinositol 4-phosphate + H2O
phosphatidylinositol + phosphate
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phosphatidylinositol 4-phosphate + H2O
phosphatidylinositol + phosphate
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the enzyme specifically hydrolyzes phosphatidylinositol 4-phosphate in vitro
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phosphatidylinositol 4-phosphate + H2O
phosphatidylinositol + phosphate
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phosphatidylinositol 4-phosphate + H2O
phosphatidylinositol + phosphate
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preferred substrate
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additional information
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the enzyme shows no activity on either phosphatidylinositol 4,5-bisphosphate or phosphatidylinositol 3,4,5-triphosphate
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Sac1, a phosphoinositide lipid phosphatase, removes the phosphate residue from the inositol head group of phosphatidylinositol-4-phosphate
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SacI is in complex with Vps74, a phosphatidylinositol 4-kinase effector
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Vps74 (a PI4K effector required to maintain residence of a subset of Golgi proteins) binds directly to the catalytic domain of Sac1. Vps74 is a sensor of Pt¬dIns4P level on medial Golgi cisternae that directs Sac1-mediated dephosphosphorylation of this pool of PtdIns4P
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Sac1 is active on PI(5)P, PI(4)P, PI(3)P, with low activity on PI(3,5)P2, and with no activity on other phosphoinositides
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Infections
Rhinovirus uses a phosphatidylinositol 4-phosphate/cholesterol counter-current for the formation of replication compartments at the ER-Golgi interface.
Myopathies, Structural, Congenital
Modeling the human MTM1 p.R69C mutation in murine Mtm1 results in exon 4 skipping and a less severe myotubular myopathy phenotype.
Neoplasms
Controlling PTEN (Phosphatase and Tensin Homolog) Stability: A DOMINANT ROLE FOR LYSINE 66.
Neoplasms
SHIP2 signaling in normal and pathological situations: Its impact on cell proliferation.
Neuromuscular Diseases
Modeling the human MTM1 p.R69C mutation in murine Mtm1 results in exon 4 skipping and a less severe myotubular myopathy phenotype.
Osteosarcoma
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.
Rhabdomyosarcoma
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.
Starvation
Growth control of Golgi phosphoinositides by reciprocal localization of sac1 lipid phosphatase and pik1 4-kinase.
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metabolism
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the enzyme regulates oxysterol-binding protein activity
malfunction
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RNAi-mediated knockdown of SAC1 causes changes in Golgi morphology and mislocalization of Golgi enzymes. Enzymes involved in glycan processing, such as mannosidase II and Nacetylglucosamine transferase I, redistribute to aberrant intracellular structures and to the cell surface in SAC1 knockdown cells. SAC1 depletion also induces a unique pattern of Golgi-specific defects in N- and O-linked glycosylation, phenotype, overview. SAC1 knockdown allows alpha2,6 sialyltransferase to more effectively compete against Core 2 transferase
malfunction
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disruption of the Sac1-Vps74 interface results in a broader distribution of phosphatidylinositol 4-phosphate within the Golgi apparatus and failure to maintain residence of a medial Golgi mannosyltransferase
malfunction
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the rate of biosynthesis of phosphatidylserine in sac1 deleted cells is significantly lower than that in wild-type cells. An abnormal phosphatidylserine distribution in sac1 deleted cells is observed when a specific probe for phosphatidylserine is expressed
malfunction
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genomic ablation of the enzyme causes perturbation on transferrin and integrin recycling as well as defects in cell migration
physiological function
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deletion of SAC1 encoding a PtdIns(4)P phosphatase, increases levels of most sphingolipid species, including sphingoid bases, sphingoid base phosphates, and phytoceramide. Deletion of SAC1 dramatically reduces inositol phosphosphingolipids, which result from the addition of a PtdIns-derived phosphoinositol head group to ceramides through Aur1p. Deletion of SAC1 decreases PtdIns dramatically in both steady-state and pulse labeling studies, suggesting that the observed effects on sphingolipids may result from modulation of the availability of PtdIns as a substrate for Aur1p
physiological function
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mutant Sac1 C392S is a potent inhibitor of fusion of coat protein complex II, COPII, vesicles with Golgi compartments whereas the Sac1 WT protein does not display an equal inhibitory effect. The inhibitory effects of Sac1 wild-type are likely due to catalytic activity of the enzyme and not due to lipid ligand binding. Pretreatment of acceptor membranes with 50 microM Sac1 wild-type also causes an accumulation of diffusible vesicles in budding reactions and strong inhibition of SNARE complex formation
physiological function
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SAC1 organizes phosphatidylinositol-4-phosphate distribution between the Golgi complex and the trans-Golgi-network, which is instrumental for resident enzyme partitioning and Golgi morphology
physiological function
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in Drosophila development, the enzyme regulates JNK signaling, attenuates Hedgehog signaling, and regulates axon guidance in the embryonic central nervous system. The enzyme is required for postembryonic synaptic maturation and neuronal cell maintenance
physiological function
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the enzyme is crucial for normal eye development and required for promoting microtubule stability
physiological function
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the enzyme is required for survival during the asexual erythrocytic stages of Plasmodium falciparum
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C458S
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catalytically inactive
D394N
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mutant is stable and displays a profile similar to that of the wild-type protein as determined by gel filtration chromatography. Mutant shows no activity
D397N
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mutant is stable and displays a profile similar to that of the wild-type protein as determined by gel filtration chromatography. Mutant shows no activity
DELTA2-460
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a truncated Sac1 mutant (Sac1(2-460), truncated at the end of the structured region) exhibits essentially no PtdIns4P phosphatase activity. In contrast to full-length version, presence of PtdIns4P in liposomes does not elicit substantial membrane binding by the truncated mutant Sac1(2-460), suggesting that residues 461-511 are important for substrate recognition
R207Q
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mutant is stable and displays a profile similar to that of the wild-type protein as determined by gel filtration chromatography. Mutant is active but with reduced allosteric kinetics compared to that of the wild-type enzyme. Mutant shows a reduced allosteric effect of the R207Q mutation which is likely due to the reduced affinity for allosteric activators
R256Q
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mutant is stable and displays a profile similar to that of the wild-type protein as determined by gel filtration chromatography. Mutant shows no activity
R398Q
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mutant is stable and displays a profile similar to that of the wild-type protein as determined by gel filtration chromatography. Mutant shows no activity
additional information
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usage of the recombinant Sac1p Sac1 phosphatase activity to deplete phosphatidylinositol-4-phosphate from semi-intact cell membranes, method development and optimization, overview
C392S
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catalytically inactive mutant
C392S
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inactive mutant does not rescue the defect of Sac1 deletion
C392S
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mutant is stable and displays a profile similar to that of the wild-type protein as determined by gel filtration chromatography. Mutant shows no activity
C392S
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mutation leads to inactivation
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Thole, J.M.; Vermeer, J.E.; Zhang, Y.; Gadella, T.W.; Nielsen, E.
Root hair defective4 encodes a phosphatidylinositol-4-phosphate phosphatase required for proper root hair development in Arabidopsis thaliana
Plant Cell
20
381-395
2008
Arabidopsis thaliana (Q9C5G5), Arabidopsis thaliana
brenda
Brice, S.E.; Alford, C.W.; Cowart, L.A.
Modulation of sphingolipid metabolism by the phosphatidylinositol-4-phosphate phosphatase Sac1p through regulation of phosphatidylinositol in Saccharomyces cerevisiae
J. Biol. Chem.
284
7588-7596
2009
Saccharomyces cerevisiae
brenda
Lorente-Rodriguez, A.; Barlowe, C.
Requirement for Golgi-localized PI(4)P in fusion of COPII vesicles with Golgi compartments
Mol. Biol. Cell
22
216-229
2011
Saccharomyces cerevisiae
brenda
Cheong, F.Y.; Sharma, V.; Blagoveshchenskaya, A.; Oorschot, V.M.; Brankatschk, B.; Klumperman, J.; Freeze, H.H.; Mayinger, P.
Spatial regulation of Golgi phosphatidylinositol-4-phosphate is required for enzyme localization and glycosylation fidelity
Traffic
11
1180-1190
2010
Homo sapiens
brenda
Zhong, S.; Hsu, F.; Stefan, C.J.; Wu, X.; Patel, A.; Cosgrove, M.S.; Mao, Y.
Allosteric activation of the phosphoinositide phosphatase Sac1 by anionic phospholipids
Biochemistry
51
3170-3177
2012
Saccharomyces cerevisiae
brenda
Cai, Y.; Deng, Y.; Horenkamp, F.; Reinisch, K.M.; Burd, C.G.
Sac1-Vps74 structure reveals a mechanism to terminate phosphoinositide signaling in the Golgi apparatus
J. Cell Biol.
206
485-491
2014
Saccharomyces cerevisiae
brenda
Wood, C.S.; Hung, C.S.; Huoh, Y.S.; Mousley, C.J.; Stefan, C.J.; Bankaitis, V.; Ferguson, K.M.; Burd, C.G.
Local control of phosphatidylinositol 4-phosphate signaling in the Golgi apparatus by Vps74 and Sac1 phosphoinositide phosphatase
Mol. Biol. Cell
23
2527-2536
2012
Saccharomyces cerevisiae
brenda
Tani, M.; Kuge, O.
Involvement of Sac1 phosphoinositide phosphatase in the metabolism of phosphatidylserine in the yeast Saccharomyces cerevisiae
Yeast
31
145-158
2014
Saccharomyces cerevisiae
brenda
Del Bel, L.M.; Griffiths, N.; Wilk, R.; Wei, H.C.; Blagoveshchenskaya, A.; Burgess, J.; Polevoy, G.; Price, J.V.; Mayinger, P.; Brill, J.A.
The phosphoinositide phosphatase Sac1 regulates cell shape and microtubule stability in the developing Drosophila eye
Development
145
151571
2018
Drosophila melanogaster
brenda
Zewe, J.P.; Wills, R.C.; Sangappa, S.; Goulden, B.D.; Hammond, G.R.
SAC1 degrades its lipid substrate PtdIns4P in the endoplasmic reticulum to maintain a steep chemical gradient with donor membranes
eLife
7
e35588
2018
Saccharomyces cerevisiae
brenda
Lim, J.M.; Park, S.; Lee, M.S.; Balla, T.; Kang, D.; Rhee, S.G.
Accumulation of PtdIns(4)P at the Golgi mediated by reversible oxidation of the PtdIns(4)P phosphatase Sac1 by H2O2
Free Radic. Biol. Med.
130
426-435
2019
Homo sapiens
brenda
Park, S.; Lim, J.M.; Park, S.H.; Kim, S.; Heo, S.; Balla, T.; Jeong, W.; Rhee, S.G.; Kang, D.
Inactivation of the PtdIns(4)P phosphatase Sac1 at the Golgi by H2O2 produced via Ca2+-dependent Duox in EGF-stimulated cells
Free Radic. Biol. Med.
131
40-49
2019
Homo sapiens
brenda
Hsu, F.; Hu, F.; Mao, Y.
Spatiotemporal control of phosphatidylinositol 4-phosphate by Sac2 regulates endocytic recycling
J. Cell Biol.
209
97-110
2015
Mus musculus
brenda
Sohn, M.; Ivanova, P.; Brown, H.A.; Toth, D.J.; Varnai, P.; Kim, Y.J.; Balla, T.
Lenz-Majewski mutations in PTDSS1 affect phosphatidylinositol 4-phosphate metabolism at ER-PM and ER-Golgi junctions
Proc. Natl. Acad. Sci. USA
113
4314-4319
2016
Saccharomyces cerevisiae
brenda
Theriault, C.; Richard, D.
Characterization of a putative Plasmodium falciparum SAC1 phosphoinositide-phosphatase homologue potentially required for survival during the asexual erythrocytic stages
Sci. Rep.
7
12710
2017
Plasmodium falciparum
brenda
Charman, M.; Goto, A.; Ridgway, N.D.
Oxysterol-binding protein recruitment and activity at the endoplasmic reticulum-Golgi interface are independent of Sac1
Traffic
18
519-529
2017
Saccharomyces cerevisiae
brenda
Del Bel, L.M.; Brill, J.A.
Sac1, a lipid phosphatase at the interface of vesicular and nonvesicular transport
Traffic
19
301-318
2018
Saccharomyces cerevisiae, Drosophila melanogaster
brenda