Sac1 is an integral ER/Golgi membrane phosphoinositide phosphatase of Saccharomyces cerevisiae (SAC domain family, orthologous to human SACM1L). It is a type II transmembrane protein whose N-terminal cytosolic SAC domain hydrolyses the 4-phosphate of PtdIns4P (its principal in vivo substrate) and also dephosphorylates PtdIns3P in vitro, with low activity on PtdIns(3,5)P2. In growing cells Sac1 is retained in the ER (including cortical ER at ER-plasma membrane contact sites) through binding to Dpm1, and it relocates to the Golgi when growth slows. At ER-PM contacts Sac1 consumes the plasma membrane PtdIns4P pool generated by Stt4, an activity stimulated by Osh proteins and VAPs; on medial Golgi cisternae it is directed by Vps74 to keep PtdIns4P low. By turning over PtdIns4P Sac1 maintains the ER-to-Golgi/PM PtdIns4P gradient that drives Osh-mediated lipid exchange, and it influences actin organisation, vacuole morphology, Golgi secretory function, dolichol-oligosaccharide synthesis, autophagosome-vacuole fusion and sphingolipid homeostasis (as a component of the SPOTS complex with serine palmitoyltransferase and Orm1/2).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000139 Golgi membrane | IDA PMID:15657391 Cell growth-dependent coordination of lipid signaling and gl... | ACCEPT | Summary: Faulhammer et al. showed Sac1 translocates to Golgi membranes when growth slows (nutrient limitation). Supporting Evidence: PMID:15657391 causing translocation of Sac1p to Golgi membranes |
| GO:0000139 Golgi membrane | IDA PMID:8314848 SAC1p is an integral membrane protein that influences the ce... | ACCEPT | Summary: Whitters et al. localized Sac1 to Golgi and ER membranes by fractionation/immunolocalization. Supporting Evidence: PMID:8314848 SAC1p is an integral membrane protein that localizes to the yeast Golgi complex and to the yeast ER |
| GO:0000139 Golgi membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt SubCell mapping to Golgi membrane; consistent with experimental data. Supporting Evidence: PMID:8314848 SAC1p is an integral membrane protein that localizes to the yeast Golgi complex and to the yeast ER |
| GO:0000139 Golgi membrane | IMP PMID:15657391 Cell growth-dependent coordination of lipid signaling and gl... | ACCEPT | Summary: IMP-based location: disrupting Dpm1 interaction alters Sac1 ER/Golgi distribution (Faulhammer et al.). Consistent with the IDA Golgi membrane data. Supporting Evidence: PMID:15657391 causing translocation of Sac1p to Golgi membranes |
| GO:0004438 phosphatidylinositol-3-phosphate phosphatase activity | IDA PMID:10625610 SAC1 encodes a regulated lipid phosphoinositide phosphatase,... | ACCEPT | Summary: Hughes et al. demonstrated Sac1 phosphoinositide phosphatase activity and its specificity in vitro; UniProt records PtdIns3P hydrolysis (EC 3.1.3.64) from this work. In vivo the dominant substrate is PtdIns4P, but PtdIns3P hydrolysis is an established activity. Supporting Evidence: PMID:10625610 We have now demonstrated this activity for Sac1p and have characterized its specificity. file:yeast/SAC1/SAC1-uniprot.txt Phosphoinositide phosphatase which catalyzes the hydrolysis |
| GO:0004438 phosphatidylinositol-3-phosphate phosphatase activity | IEA GO_REF:0000120 | ACCEPT | Summary: EC 3.1.3.64/RHEA:12316 mapping, derived from the UniProt catalytic activity based on Hughes et al.; correct. Supporting Evidence: file:yeast/SAC1/SAC1-uniprot.txt Phosphoinositide phosphatase which catalyzes the hydrolysis |
| GO:0004438 phosphatidylinositol-3-phosphate phosphatase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways PWY3O-242 assigns Sac1 to PI3P + H2O -> PI (EC 3.1.3.64). Supported in vitro and by an ER PtdIns3P pool controlled by Sac1, although Ymr1/Sjl2/Sjl3 are the main PI3P phosphatases in vivo. Supporting Evidence: PMID:10625610 We have now demonstrated this activity for Sac1p and have characterized its specificity. PMID:11792713 Sac1p controls a pool of phosphatidylinositol 3-phosphate and phosphatidylinositol 4-phosphate in the ER |
| GO:0005515 protein binding | IPI PMID:21295699 Osh proteins regulate phosphoinositide metabolism at ER-plas... | REMOVE | Summary: Osh3 (P38713) interaction (Stefan et al.); Osh proteins stimulate Sac1 phosphatase activity at ER-PM contact sites. Genuine and functionally relevant, but bare 'protein binding' is uninformative; removal does not dispute the interaction, which is captured in the description. Supporting Evidence: PMID:21295699 We reconstitute Osh protein-stimulated Sac1 PI phosphatase activity in vitro. |
| GO:0005739 mitochondrion | HDA PMID:14576278 The proteome of Saccharomyces cerevisiae mitochondria. | MARK AS OVER ANNOTATED | Summary: Mitochondrial proteome HTP hit. Sac1 is an ER/Golgi integral membrane protein; ER membranes commonly co-purify with mitochondria and no mitochondrial role is known. Supporting Evidence: PMID:11514624 the majority of Sac1p localizes to the endoplasmic reticulum, and this localization is crucial for the efficient turnover of PtdIns(4)P |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | MARK AS OVER ANNOTATED | Summary: PROMITO mitochondrial proteome HTP hit; likely ER contamination, as above. Supporting Evidence: PMID:11514624 the majority of Sac1p localizes to the endoplasmic reticulum, and this localization is crucial for the efficient turnover of PtdIns(4)P |
| GO:0005741 mitochondrial outer membrane | HDA PMID:16407407 Proteomic analysis of the yeast mitochondrial outer membrane... | MARK AS OVER ANNOTATED | Summary: Outer mitochondrial membrane proteome HTP hit; likely ER/mitochondria contact contamination. No supporting low-throughput evidence. Supporting Evidence: PMID:11514624 the majority of Sac1p localizes to the endoplasmic reticulum, and this localization is crucial for the efficient turnover of PtdIns(4)P |
| GO:0005783 endoplasmic reticulum | HDA PMID:26928762 One library to make them all: streamlining the creation of y... | ACCEPT | Summary: HTP GFP-library localization to ER; consistent with low-throughput data. Supporting Evidence: PMID:11514624 the majority of Sac1p localizes to the endoplasmic reticulum, and this localization is crucial for the efficient turnover of PtdIns(4)P |
| GO:0005783 endoplasmic reticulum | IBA GO_REF:0000033 | ACCEPT | Summary: IBA ER localization from the SACM1L clade; well supported for yeast Sac1. Supporting Evidence: PMID:11514624 the majority of Sac1p localizes to the endoplasmic reticulum, and this localization is crucial for the efficient turnover of PtdIns(4)P |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:11514624 Sac1 lipid phosphatase and Stt4 phosphatidylinositol 4-kinas... | ACCEPT | Summary: Foti et al. showed the majority of Sac1 resides in the ER and that ER localization is needed for PtdIns4P turnover. Supporting Evidence: PMID:11514624 the majority of Sac1p localizes to the endoplasmic reticulum, and this localization is crucial for the efficient turnover of PtdIns(4)P |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:15657391 Cell growth-dependent coordination of lipid signaling and gl... | ACCEPT | Summary: Faulhammer et al.: C-terminal region targets Sac1 to the ER via Dpm1 binding during growth. Supporting Evidence: PMID:15657391 a COOH-terminal region in yeast Sac1p is crucial for ER targeting by directly interacting with dolicholphosphate mannose synthase Dpm1p |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:8314848 SAC1p is an integral membrane protein that influences the ce... | ACCEPT | Summary: Whitters et al.: Sac1 is an integral membrane protein of the ER and Golgi. Supporting Evidence: PMID:8314848 SAC1p is an integral membrane protein that localizes to the yeast Golgi complex and to the yeast ER |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt SubCell mapping to ER membrane; correct. Supporting Evidence: file:yeast/SAC1/SAC1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | IMP PMID:11514624 Sac1 lipid phosphatase and Stt4 phosphatidylinositol 4-kinas... | ACCEPT | Summary: Foti et al. (IMP): membrane localization of Sac1 in the ER is required for PtdIns4P turnover. Supporting Evidence: PMID:11514624 the majority of Sac1p localizes to the endoplasmic reticulum, and this localization is crucial for the efficient turnover of PtdIns(4)P |
| GO:0005789 endoplasmic reticulum membrane | IMP PMID:11792713 Retention of the yeast Sac1p phosphatase in the endoplasmic ... | ACCEPT | Summary: Konrad et al. (IMP): topology mapping and an ER-retained mutant define Sac1 as an ER type II transmembrane protein. Supporting Evidence: PMID:11792713 Sac1p is a type II transmembrane protein with a large N-terminal cytosolic domain |
| GO:0005789 endoplasmic reticulum membrane | IMP PMID:15657391 Cell growth-dependent coordination of lipid signaling and gl... | ACCEPT | Summary: Faulhammer et al. (IMP): mutation of the Dpm1-binding region alters ER retention. Supporting Evidence: PMID:15657391 a COOH-terminal region in yeast Sac1p is crucial for ER targeting by directly interacting with dolicholphosphate mannose synthase Dpm1p |
| GO:0005797 Golgi medial cisterna | IDA PMID:22553352 Local control of phosphatidylinositol 4-phosphate signaling ... | KEEP AS NON CORE | Summary: Wood et al. showed Vps74 binds the Sac1 catalytic domain and that Sac1 keeps PtdIns4P low on medial Golgi cisternae. Real but specialised location; retained as non-core. Supporting Evidence: PMID:22553352 These results indicate that both Vps74 and Sac1 function to maintain a low level of PtdIns4P on medial Golgi compartments. PMID:22553352 Vps74 binds directly to the catalytic domain of Sac1 |
| GO:0005829 cytosol | RCA GO_REF:0000123 | MODIFY | Summary: YeastPathways RCA default 'cytosol'. Sac1 is an integral ER membrane protein whose cytosol-facing catalytic domain acts on membrane lipids; the location of activity is the ER membrane. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: PMID:11792713 Sac1p is a type II transmembrane protein with a large N-terminal cytosolic domain |
| GO:0016791 phosphatase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro SAC domain mapping to generic 'phosphatase activity'; the specific activity is PtdIns4P phosphatase. Proposed replacements: phosphatidylinositol-4-phosphate phosphatase activity Supporting Evidence: PMID:11792713 Sac1p is an important 4-phosphatase in the ER |
| GO:0017059 serine palmitoyltransferase complex | IDA PMID:20182505 Orm family proteins mediate sphingolipid homeostasis. | KEEP AS NON CORE | Summary: Breslow et al. identified Sac1 by MS in the SPOTS complex with Lcb1/Lcb2/Tsc3/Orm1/2 and showed Sac1 binds Lcb1/2 independently of Orm. Genuine complex membership reflecting a regulatory role in sphingolipid synthesis; non-core. Supporting Evidence: PMID:20182505 Mass spectrometry showed that this complex comprises the serine palmitoyltransferase proteins Lcb1, Lcb2 and Tsc3, in addition to the phosphoinositide phosphatase Sac1 PMID:20182505 These findings together suggest that Sac1 modulates serine palmitoyltransferase activity directly, but in a mode distinct from Orm1/2. |
| GO:0017059 serine palmitoyltransferase complex | IPI PMID:20182505 Orm family proteins mediate sphingolipid homeostasis. | KEEP AS NON CORE | Summary: IPI version of the SPOTS complex membership (Breslow et al.). Supporting Evidence: PMID:20182505 Mass spectrometry showed that this complex comprises the serine palmitoyltransferase proteins Lcb1, Lcb2 and Tsc3, in addition to the phosphoinositide phosphatase Sac1 |
| GO:0032541 cortical endoplasmic reticulum | IDA PMID:30785834 The P5A ATPase Spf1p is stimulated by phosphatidylinositol 4... | ACCEPT | Summary: Endogenously tagged Sac1 is mainly in the PM-associated cortical ER (Sorensen et al.), consistent with its action on plasma membrane PtdIns4P at ER-PM contact sites. Supporting Evidence: PMID:30785834 while Sac1p is mainly found in the PM-associated part of the cortical ER |
| GO:0036092 phosphatidylinositol-3-phosphate biosynthetic process | IEA GO_REF:0000108 | REMOVE | Summary: GO_REF:0000108 inference from the RCA 'PtdIns(3,5)P2 5-phosphatase activity' (product PtdIns3P). Sac1 consumes rather than produces PtdIns3P (it hydrolyses PtdIns3P to PI), its activity on PtdIns(3,5)P2 is low, and the physiological PtdIns(3,5)P2 5-phosphatase in yeast is Fig4. A PtdIns3P biosynthetic role for Sac1 is not supported. Supporting Evidence: file:yeast/SAC1/SAC1-uniprot.txt Has low activity towards phosphatidylinositol-3,5- PMID:10625610 We have now demonstrated this activity for Sac1p and have characterized its specificity. |
| GO:0043812 phosphatidylinositol-4-phosphate phosphatase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA PtdIns4P phosphatase from the SACM1L clade; consistent with extensive yeast data. Supporting Evidence: PMID:11792713 Sac1p is an important 4-phosphatase in the ER PMID:11514624 inactivation of Sac1p leads to a specific increase in the cellular levels of phosphatidylinositol 4-phosphate (PtdIns(4)P) |
| GO:0043812 phosphatidylinositol-4-phosphate phosphatase activity | IDA PMID:10625610 SAC1 encodes a regulated lipid phosphoinositide phosphatase,... | ACCEPT | Summary: Hughes et al. characterised Sac1 phosphatase specificity in vitro; sac1 mutants accumulate PtdIns4P. Supporting Evidence: PMID:10625610 We have now demonstrated this activity for Sac1p and have characterized its specificity. PMID:10625610 resulting in altered levels of all lipid phos- phoinositides, particularly phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate |
| GO:0043812 phosphatidylinositol-4-phosphate phosphatase activity | IDA PMID:11792713 Retention of the yeast Sac1p phosphatase in the endoplasmic ... | ACCEPT | Summary: Konrad et al.: ER-retained Sac1 alters phosphoinositide levels; Sac1 is the major ER 4-phosphatase. Supporting Evidence: PMID:11792713 Sac1p is an important 4-phosphatase in the ER |
| GO:0043812 phosphatidylinositol-4-phosphate phosphatase activity | IEA GO_REF:0000116 | ACCEPT | Summary: RHEA:55652 mapping (PI4P + H2O -> PI); correct core reaction. Supporting Evidence: file:yeast/SAC1/SAC1-uniprot.txt Phosphoinositide phosphatase which catalyzes the hydrolysis |
| GO:0043813 phosphatidylinositol-3,5-bisphosphate 5-phosphatase activity | RCA GO_REF:0000123 | MARK AS OVER ANNOTATED | Summary: YeastPathways assigns Sac1 to a PtdIns(3,5)P2 dephosphorylation step mapped to the 5-phosphatase term. Sac1 has only low in vitro activity on PtdIns(3,5)P2, SGD curated that activity as a 3-phosphatase from the same data, and Fig4 (with Fab1/Vac14) is the physiological PtdIns(3,5)P2 5-phosphatase. Likely YeastCyc over-assignment of a minor in vitro activity. Supporting Evidence: file:yeast/SAC1/SAC1-uniprot.txt Has low activity towards phosphatidylinositol-3,5- |
| GO:0046854 phosphatidylinositol phosphate biosynthetic process | RCA GO_REF:0000123 | MODIFY | Summary: YeastPathways RCA places all PWY3O-242 enzymes in 'phosphatidylinositol phosphate biosynthetic process'. Sac1 removes phosphate from PtdIns4P/PtdIns3P to give PI; its process is phosphatidylinositol dephosphorylation (already annotated), not PIP biosynthesis. Proposed replacements: phosphatidylinositol dephosphorylation Supporting Evidence: PMID:11514624 inactivation of Sac1p leads to a specific increase in the cellular levels of phosphatidylinositol 4-phosphate (PtdIns(4)P) |
| GO:0046856 phosphatidylinositol dephosphorylation | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from the SACM1L clade. Sac1 is a phosphoinositide phosphatase whose main role is PtdIns4P dephosphorylation. Supporting Evidence: PMID:11792713 Sac1p is an important 4-phosphatase in the ER |
| GO:0046856 phosphatidylinositol dephosphorylation | IDA PMID:10625610 SAC1 encodes a regulated lipid phosphoinositide phosphatase,... | ACCEPT | Summary: In vitro phosphatase activity (Hughes et al.). Sac1 is a phosphoinositide phosphatase whose main role is PtdIns4P dephosphorylation. Supporting Evidence: PMID:10625610 We have now demonstrated this activity for Sac1p and have characterized its specificity. |
| GO:0046856 phosphatidylinositol dephosphorylation | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA mapping. Sac1 is a phosphoinositide phosphatase whose main role is PtdIns4P dephosphorylation. Supporting Evidence: file:yeast/SAC1/SAC1-uniprot.txt Phosphoinositide phosphatase which catalyzes the hydrolysis |
| GO:0046856 phosphatidylinositol dephosphorylation | IGI PMID:10625610 SAC1 encodes a regulated lipid phosphoinositide phosphatase,... | ACCEPT | Summary: IGI: the SAC-domain paralog Inp52/Sjl2 (with/from SGD:S000005050) restores phosphoinositide levels in sac1 mutants. Sac1 is a phosphoinositide phosphatase whose main role is PtdIns4P dephosphorylation. Supporting Evidence: PMID:10625610 We have identified two proteins with homology to Sac1p that can suppress drug sensitivity and also restore the levels of the phosphoinositides in sac1 mutants. |
| GO:0046856 phosphatidylinositol dephosphorylation | IGI PMID:10625610 SAC1 encodes a regulated lipid phosphoinositide phosphatase,... | ACCEPT | Summary: IGI: suppression by the SAC-domain paralog Inp53/Sjl3 (with/from SGD:S000005635) of sac1 phosphoinositide defects. Sac1 is a phosphoinositide phosphatase whose main role is PtdIns4P dephosphorylation. Supporting Evidence: PMID:10625610 We have identified two proteins with homology to Sac1p that can suppress drug sensitivity and also restore the levels of the phosphoinositides in sac1 mutants. |
| GO:0046856 phosphatidylinositol dephosphorylation | IMP PMID:10625610 SAC1 encodes a regulated lipid phosphoinositide phosphatase,... | ACCEPT | Summary: sac1 mutants have altered phosphoinositide levels, especially PtdIns4P. Sac1 is a phosphoinositide phosphatase whose main role is PtdIns4P dephosphorylation. Supporting Evidence: PMID:10625610 resulting in altered levels of all lipid phos- phoinositides, particularly phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate |
| GO:0046856 phosphatidylinositol dephosphorylation | IMP PMID:22553352 Local control of phosphatidylinositol 4-phosphate signaling ... | ACCEPT | Summary: sac1 cells have elevated PtdIns4P on medial Golgi cisternae (Wood et al.). Sac1 is a phosphoinositide phosphatase whose main role is PtdIns4P dephosphorylation. Supporting Evidence: PMID:22553352 These results indicate that both Vps74 and Sac1 function to maintain a low level of PtdIns4P on medial Golgi compartments. |
| GO:0052629 phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity | IDA PMID:10625610 SAC1 encodes a regulated lipid phosphoinositide phosphatase,... | KEEP AS NON CORE | Summary: Hughes et al. detected low Sac1 activity on PtdIns(3,5)P2 in vitro, curated as 3-phosphatase. Minor activity of uncertain physiological relevance (Fig4 is the main PtdIns(3,5)P2 phosphatase). Supporting Evidence: file:yeast/SAC1/SAC1-uniprot.txt Has low activity towards phosphatidylinositol-3,5- |
| GO:0061909 autophagosome-lysosome fusion | IMP PMID:32693712 PtdIns4P restriction by hydrolase SAC1 decides specific fusi... | KEEP AS NON CORE | Summary: Sac1 was identified in a yeast screen as required for autophagosome-vacuole fusion through its PtdIns4P phosphatase activity (excess Golgi PtdIns4P on Atg9 vesicles blocks SNARE recruitment). Indirect role; non-core. Supporting Evidence: PMID:32693712 we identified Sac1 by a high throughput screen in Saccharomyces cerevisiae to show it was critical for autophagosome-lysosome fusion through its PtdIns4P phosphatase activity |
| GO:0072517 host cell viral assembly compartment | IMP PMID:32269127 Co-opted Cellular Sac1 Lipid Phosphatase and PI(4)P Phosphoi... | KEEP AS NON CORE | Summary: Sac1 is co-opted by tomato bushy stunt virus and is found in the viral replication compartment in yeast. A host-pathogen location, not part of normal Sac1 biology; non-core. Supporting Evidence: PMID:32269127 its presence in the virus-induced membrane contact sites and within the TBSV replication compartment |
| GO:0090156 intracellular sphingolipid homeostasis | NAS PMID:20182505 Orm family proteins mediate sphingolipid homeostasis. | KEEP AS NON CORE | Summary: Sac1 deletion raises long-chain base levels and Sac1 is a SPOTS complex component, linking it to sphingolipid homeostasis. Supported (NAS) but secondary to PtdIns4P turnover. Supporting Evidence: PMID:20182505 Deletion of SAC1 leads to elevated LCB levels PMID:20182505 These findings together suggest that Sac1 modulates serine palmitoyltransferase activity directly, but in a mode distinct from Orm1/2. |
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Download this section (compressed HTML)Phosphatidylinositol phosphate phosphatase; role in early and medial Golgi PtdIns4P hydrolysis; regulated by Vps74p interaction; ER localized transmembrane protein which cycles through the Golgi; role in protein trafficking, processing, secretion, and cell wall maintenance; regulates sphingolipid biosynthesis by modulating PtdIns(4)P metabolism; PtdIns4P PPase activity is crucial for autophagosome-vacuole fusion during autophagy; human homolog SACM1L complements autophagy defects of the null
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