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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 (16, 3, 13). 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 (4, 16, 13 and references therein). Localization of Sac1p is regulated by growth conditions as well as interactions with proteins such as Dpm1p (17). Expression of SAC1 is regulated in response to changing levels of PtdIns[4]P (18).

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 (6). 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 (6, 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 11). PtdInsPs are also precursors of the water-soluble inositol phosphates (IPs), an important class of intracellular signaling molecules (reviewed in 12, 14 and 15).

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 (11, 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.", "date_edited": "2008-06-26"}, "literature_overview": {"primary_count": 87, "additional_count": 80, "review_count": 51, "go_count": 15, "phenotype_count": 35, "disease_count": 0, "interaction_count": 131, "regulation_count": 2, "ptm_count": 5, "funComplement_count": 1, "htp_count": 79, "total_count": 374}, "disease_overview": {"manual_disease_terms": [], "htp_disease_terms": [], "computational_annotation_count": 0, "date_last_reviewed": null}, "ecnumbers": [{"display_name": "3.1.3.64", "link": "/ecnumber/EC:3.1.3.64"}], "URS_ID": null, "main_strain": "S288C", "genetic_position": -153.8, "regulation_overview": {"regulator_count": 6, "target_count": 0}, "reference_mapping": {"552023": 1, "600779": 2, "645278": 3, "564119": 4, "629925": 5, "648891": 6, "478135": 7, "394014": 8, "2218025": 9, "503360": 10, "575124": 11, "502465": 12, "586006": 13, "493843": 14, "501717": 15, "502727": 16, "534667": 17, "492141": 18, "617384": 19}, "history": [{"category": "Name", "history_type": "LSP", "note": "Name: RSD1", "date_created": "2010-02-16", "references": [{"id": 617384, "display_name": "Cleves AE, et al. (1989)", "citation": "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", "pubmed_id": 2687291, "link": "/reference/S000050014", "year": 1989, "urls": [{"display_name": "DOI full text", "link": "http://dx.doi.org/10.1083/jcb.109.6.2939"}, {"display_name": "PMC full text", "link": "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2115899/"}, {"display_name": "PubMed", "link": "http://www.ncbi.nlm.nih.gov/pubmed/2687291"}]}]}, {"category": "Name", "history_type": "LSP", "note": "Name: SAC1", "date_created": "2000-05-19", "references": [{"id": 552023, "display_name": "Mortimer RK, et al. (1989)", "citation": "Mortimer RK, et al. (1989) Genetic map of Saccharomyces cerevisiae, edition 10. Yeast 5(5):321-403", "pubmed_id": 2678811, "link": "/reference/S000073208", "year": 1989, "urls": [{"display_name": "DOI full text", "link": "http://dx.doi.org/10.1002/yea.320050503"}, {"display_name": "PubMed", "link": "http://www.ncbi.nlm.nih.gov/pubmed/2678811"}]}]}], "complexes": [{"format_name": "CPX-3158", "display_name": "SPOTS complex"}]}, tabs: {"id": 1268650, "protein_tab": true, "interaction_tab": true, "summary_tab": true, "go_tab": true, "sequence_section": true, "expression_tab": true, "phenotype_tab": true, "literature_tab": true, "wiki_tab": false, "regulation_tab": true, "sequence_tab": true, "history_tab": true, "homology_tab": true, "disease_tab": false} }; SAC1 | SGD

SAC1 / YKL212W Overview


Standard Name
SAC1 1
Systematic Name
YKL212W
SGD ID
SGD:S000001695
Aliases
RSD1 19
Feature Type
ORF , Verified
Description
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 2 3 4 5 7 8 9
Name Description
Suppressor of ACtin 6
Comparative Info
Sequence Details

Sequence

The S. cerevisiae Reference Genome sequence is derived from laboratory strain S288C. Download DNA or protein sequence, view genomic context and coordinates. Click "Sequence Details" to view all sequence information for this locus, including that for other strains.


Protein Details

Protein

Basic sequence-derived (length, molecular weight, isoelectric point) and experimentally-determined (median abundance, median absolute deviation) protein information. Click "Protein Details" for further information about the protein such as half-life, abundance, domains, domains shared with other proteins, protein sequence retrieval for various strains, physico-chemical properties, protein modification sites, and external identifiers for the protein.


Length (a.a.)
623
Mol. Weight (Da)
71125.2
Isoelectric Point
7.8
Median Abundance (molecules/cell)
10996 +/- 2810
Half-life (hr)
11.2

Alleles

Curated mutant alleles for the specified gene, listed alphabetically. Click on the allele name to open the allele page. Click "SGD search" to view all alleles in search results.


View all SAC1 alleles in SGD search

Gene Ontology Details

Gene Ontology

GO Annotations consist of four mandatory components: a gene product, a term from one of the three Gene Ontology (GO) controlled vocabularies (Molecular Function, Biological Process, and Cellular Component), a reference, and an evidence code. SGD has manually curated and high-throughput GO Annotations, both derived from the literature, as well as computational, or predicted, annotations. Click "Gene Ontology Details" to view all GO information and evidence for this locus as well as biological processes it shares with other genes.


Summary
Phosphatidylinositol phosphate phosphatase; involved in the hydrolysis of PI3P, PI4P, and PI(3,5)P2; localizes as an integral membrane protein to the endoplasmic reticulum, and Golgi apparatus

View computational annotations

Biological Process

Manually Curated

Complex

Macromolecular complex annotations are imported from the Complex Portal. These annotations have been derived from physical molecular interaction evidence extracted from the literature and cross-referenced in the entry, or by curator inference from information on homologs in closely related species or by inference from scientific background.


Pathways


Phenotype Details

Phenotype

Phenotype annotations for a gene are curated single mutant phenotypes that require an observable (e.g., "cell shape"), a qualifier (e.g., "abnormal"), a mutant type (e.g., null), strain background, and a reference. In addition, annotations are classified as classical genetics or high-throughput (e.g., large scale survey, systematic mutation set). Whenever possible, allele information and additional details are provided. Click "Phenotype Details" to view all phenotype annotations and evidence for this locus as well as phenotypes it shares with other genes.


Summary
Non-essential gene in reference strain S288C; null mutation affects phosphatidylinositol phosphate pools and leads to abnormal actin cytoskeleton, defects in protein secretion, endocytosis and vacuolar transport, increased sensitivity to low temperatures, cell wall-affecting drugs (caffeine, Calcofluor White) and multiple other chemicals; mutations cause inositol auxotrophy
Interaction Details

Interaction

Interaction annotations are curated by BioGRID and include physical or genetic interactions observed between at least two genes. An interaction annotation is composed of the interaction type, name of the interactor, assay type (e.g., Two-Hybrid), annotation type (e.g., manual or high-throughput), and a reference, as well as other experimental details. Click "Interaction Details" to view all interaction annotations and evidence for this locus, including an interaction visualization.


1666 total interactions for 1098 unique genes

Physical Interactions

  • Affinity Capture-MS: 79
  • Affinity Capture-RNA: 3
  • Affinity Capture-Western: 9
  • Biochemical Activity: 2
  • Co-crystal Structure: 1
  • Co-localization: 1
  • Co-purification: 6
  • Far Western: 1
  • PCA: 12
  • Proximity Label-MS: 1
  • Reconstituted Complex: 2
  • Two-hybrid: 4

Genetic Interactions

  • Dosage Lethality: 2
  • Dosage Rescue: 15
  • Negative Genetic: 1200
  • Phenotypic Enhancement: 13
  • Phenotypic Suppression: 10
  • Positive Genetic: 213
  • Synthetic Growth Defect: 40
  • Synthetic Haploinsufficiency: 1
  • Synthetic Lethality: 34
  • Synthetic Rescue: 17
Regulation Details

Regulation

The number of putative Regulators (genes that regulate it) and Targets (genes it regulates) for the given locus, based on experimental evidence. This evidence includes data generated through high-throughput techniques. Click "Regulation Details" to view all regulation annotations, shared GO enrichment among regulation Targets, and a regulator/target diagram for the locus.


Regulators
6
Targets
0
Expression Details

Expression

Expression data are derived from records contained in the Gene Expression Omnibus (GEO), and are first log2 transformed and normalized. Referenced datasets may contain one or more condition(s), and as a result there may be a greater number of conditions than datasets represented in a single clickable histogram bar. The histogram division at 0.0 separates the down-regulated (green) conditions and datasets from those that are up-regulated (red). Click "Expression Details" to view all expression annotations and details for this locus, including a visualization of genes that share a similar expression pattern.


Summary Paragraph

A summary of the locus, written by SGD Biocurators following a thorough review of the literature. Links to gene names and curated GO terms are included within the Summary Paragraphs.


Last Updated: 2008-06-26

Literature Details

Literature

All manually curated literature for the specified gene, organized into topics according to their relevance to the gene (Primary Literature, Additional Literature, or Review). Click "Literature Details" to view all literature information for this locus, including shared literature between genes.


Primary
87
Additional
80
Reviews
51

Resources


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