SAC1/YKL212W Summary Help

Standard Name SAC1 1
Systematic Name YKL212W
Alias RSD1 2
Feature Type ORF, Verified
Description Phosphatidylinositol phosphate (PtdInsP) phosphatase; involved in hydrolysis of PtdIns[4]P in the early and medial Golgi; regulated by interaction with Vps74p; ER localized transmembrane protein which cycles through the Golgi; involved in protein trafficking and processing, secretion, and cell wall maintenance; regulates sphingolipid biosynthesis through the modulation of PtdIns(4)P metabolism (3, 4, 5, 6, 7, 8 and see Summary Paragraph)
Name Description Suppressor of ACtin 9
Chromosomal Location
ChrXI:34543 to 36414 | ORF Map | GBrowse
Genetic position: -153.8 cM
Gene Ontology Annotations All SAC1 GO evidence and references
  View Computational GO annotations for SAC1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 6 genes
Classical genetics
Large-scale survey
960 total interaction(s) for 613 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 48
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 8
  • Biochemical Activity: 2
  • Co-localization: 1
  • Far Western: 1
  • PCA: 12
  • Reconstituted Complex: 1
  • Two-hybrid: 3

Genetic Interactions
  • Dosage Lethality: 2
  • Dosage Rescue: 8
  • Negative Genetic: 681
  • Phenotypic Enhancement: 10
  • Phenotypic Suppression: 6
  • Positive Genetic: 104
  • Synthetic Growth Defect: 28
  • Synthetic Haploinsufficiency: 1
  • Synthetic Lethality: 26
  • Synthetic Rescue: 17

Expression Summary
Length (a.a.) 623
Molecular Weight (Da) 71,124
Isoelectric Point (pI) 7.75
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrXI:34543 to 36414 | ORF Map | GBrowse
Genetic position: -153.8 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..1872 34543..36414 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000001695

SAC1 encodes a lipid phosphatase that is involved in many cellular processes, such as cell wall maintenance and membrane and protein trafficking, through regulating levels of phosphotidylinositol (PtdIns) phosphates (reviewed in 10). Although Sac1p is able to dephosphorylate PtdIns[3]P, PtdIns[4]P, and PtdIns[3,5]P2 in vitro, the role of Sac1p in processes involving PtdIns[4]P has been the primary focus of in vivo studies (4, reviewed in 10). Sac1p specifically acts upon PtdIns(4)P produced by the PtdIns 4-kinase Stt4p and acts as antagonist to the PtdIns 4-kinase Pik1p (11, 6).

Sac1p is a type II transmembrane protein that localizes to the Golgi and the ER. This subcompartmentalization of the phosphatase determines which processes it regulates (12, 3, 11). Golgi-localized Sac1p is involved in Golgi trafficking and cell wall maintenance, while ER-localized Sac1p participates in ATP uptake into the ER, ER-based secretion and protein processing, and vacuolar function (6, 12, 11 and references therein). Localization of Sac1p is regulated by growth conditions as well as interactions with proteins such as Dpm1p (13). Expression of SAC1 is regulated in response to changing levels of PtdIns[4]P (14).

SAC1 was originally identified as a suppressor of the temperature-conditional act1-1 allele, and thus some of the phenotypes seen in the sac1 mutant are similar to those of actin mutants, such as defects in actin cytoskeleton polarization and abnormal chitin deposition (9). sac1 null phenotypes also include cold sensitivity, inositol auxotrophy, fragmented vacuoles, accumulation of lipid droplets, elevated levels of PtdIns[4]P, calcofluor white sensitivity, and constitutively-activated unfolded protein response (9, and reviewed in 10).

Sac1p is the founding member of a family of PtdIns phosphatases that share a catalytic domain known as the Sac1-like domain. In S. cerevisiae, this family includes the phosphatases Fig4p, Inp51p, Inp52p, and Inp53p, all of partially overlapping function. All of the Sac1-like domain containing proteins are highly conserved from yeast to human; mammalian members of this protein family include synaptojanin-1 (SYNJ1) and synaptojanin -2 (SYNJ2) (reviewed in 10).

About Phosphatidylinositol Phosphate Biosynthesis

The phosphorylated products of phosphatidylinositol (PtdIns, PI), collectively referred to as phosphoinositides or phosphatidylinositol phosphates (PtdInsPs, PIPs), are membrane-bound lipids that function as structural components of membranes, as well as regulators of many cellular processes in eukaryotes, including vesicle-mediated membrane trafficking, cell wall integrity, and actin cytoskeleton organization (reviewed in 10 and 15). PtdInsPs are also precursors of the water-soluble inositol phosphates (IPs), an important class of intracellular signaling molecules (reviewed in 16, 17 and 18).

The inositol ring of the membrane phospholipids and the water-soluble IPs are readily phosphorylated and dephosphorylated at a number of positions making them well suited as key regulators. PtdIns can be phosphorylated at one or a combination of positions (3', 4', or 5') on the inositol headgroup, generating a set of unique stereoisomers that have specific biological functions (reviewed in 10). These stereoisomers have been shown to be restricted to certain membranes (reviewed in 10). Phosphatidylinositol 4-phosphate (PtdIns4P) is the major PtdInsP species of the Golgi apparatus, where it plays a role in the vesicular trafficking of secretory proteins from the Golgi to the plasma membrane (reviewed in 10). Phosphatidylinositol 4,5-bisphosphate (PtdIns[4,5]P2) is the major species found at the plasma membrane and is involved in the regulation of actin cytoskeleton organization, as well as cell wall integrity, and heat shock response pathways (reviewed in 10). Phosphatidylinositol 3-phosphate (PtdIns3P) is found predominantly at endosomal membranes and in multivesicular bodies (MVB), where it plays a role in endosomal and vacuolar membrane trafficking. Phosphatidylinositol 3,5-bisphosphate (PtdIns[3,5]P2) is found on vacuolar membranes where it plays an important role in the MVB sorting pathway (reviewed in 10).

Phosphorylation and dephosphorylation of the inositol headgroups of PtdInsPs at specific membrane locations signals the recruitment of certain proteins essential for vesicular transport (15, and reviewed in 10). PtdInsPs recruit proteins that contain PtdInsP-specific binding domains, such as the well-studied pleckstrin homology (PH) domain that recognizes the phosphorylation pattern of specific PtdInsP inositol headgroups (reviewed in 10).

A number of kinases and phosphatases are involved in the generation and interconversions of PtdInsPs, the majority of which have been well conserved during evolution (reviewed in 10). The PtdInsP kinases, in contrast to the lipid phosphatases, have a higher degree of specificity. While each kinase appears to phosphorylate only one substrate, many of the lipid phosphatases can dephosphorylate a number of substrates.

Last updated: 2008-05-08 Contact SGD

References cited on this page View Complete Literature Guide for SAC1
1) Drubin, D. and Botstein, D.  (1989) Personal Communication, Mortimer Map Edition 10
2) Cleves AE, et al.  (1989) Mutations in the SAC1 gene suppress defects in yeast Golgi and yeast actin function. J Cell Biol 109(6 Pt 1):2939-50
3) Whitters EA, et al.  (1993) SAC1p is an integral membrane protein that influences the cellular requirement for phospholipid transfer protein function and inositol in yeast. J Cell Biol 122(1):79-94
4) Guo S, et al.  (1999) SAC1-like domains of yeast SAC1, INP52, and INP53 and of human synaptojanin encode polyphosphoinositide phosphatases. J Biol Chem 274(19):12990-5
5) Hughes WE, et al.  (2000) SAC1 encodes a regulated lipid phosphoinositide phosphatase, defects in which can be suppressed by the homologous Inp52p and Inp53p phosphatases. J Biol Chem 275(2):801-8
6) Schorr M, et al.  (2001) The phosphoinositide phosphatase Sac1p controls trafficking of the yeast Chs3p chitin synthase. Curr Biol 11(18):1421-6
7) Brice SE, et al.  (2009) Modulation of Sphingolipid Metabolism by the Phosphatidylinositol-4-phosphate Phosphatase Sac1p through Regulation of Phosphatidylinositol in Saccharomyces cerevisiae. J Biol Chem 284(12):7588-96
8) Wood CS, et al.  (2012) Local control of phosphatidylinositol 4-phosphate signaling in the Golgi apparatus by Vps74 and Sac1 phosphoinositide phosphatase. Mol Biol Cell 23(13):2527-36
9) Novick P, et al.  (1989) Suppressors of yeast actin mutations. Genetics 121(4):659-74
10) Strahl T and Thorner J  (2007) Synthesis and function of membrane phosphoinositides in budding yeast, Saccharomyces cerevisiae. Biochim Biophys Acta 1771(3):353-404
11) Foti M, et al.  (2001) 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 12(8):2396-411
12) Konrad G, et al.  (2002) 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 277(12):10547-54
13) Faulhammer F, et al.  (2005) Cell growth-dependent coordination of lipid signaling and glycosylation is mediated by interactions between Sac1p and Dpm1p. J Cell Biol 168(2):185-91
14) Knodler A, et al.  (2008) Expression of yeast lipid phosphatase Sac1p is regulated by phosphatidylinositol-4-phosphate. BMC Mol Biol 9:16
15) De Camilli P, et al.  (1996) Phosphoinositides as regulators in membrane traffic. Science 271(5255):1533-9
16) York JD  (2006) Regulation of nuclear processes by inositol polyphosphates. Biochim Biophys Acta 1761(5-6):552-9
17) Bennett M, et al.  (2006) Inositol pyrophosphates: metabolism and signaling. Cell Mol Life Sci 63(5):552-64
18) Bhandari R, et al.  (2007) Inositol pyrophosphate pyrotechnics. Cell Metab 5(5):321-3