FKS1/YLR342W Summary Help

Standard Name FKS1 1
Systematic Name YLR342W
Alias CND1 2 , CWH53 , ETG1 , GSC1 , PBR1
Feature Type ORF, Verified
Description Catalytic subunit of 1,3-beta-D-glucan synthase; functionally redundant with alternate catalytic subunit Gsc2p; binds to regulatory subunit Rho1p; involved in cell wall synthesis and maintenance; localizes to sites of cell wall remodeling; FKS1 has a paralog, GSC2, that arose from the whole genome duplication (3, 4, 5, 6 and see Summary Paragraph)
Name Description FK506 Sensitivity 1
Chromosomal Location
ChrXII:809997 to 815627 | ORF Map | GBrowse
Gbrowse
Gene Ontology Annotations All FKS1 GO evidence and references
  View Computational GO annotations for FKS1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 9 genes
Resources
Classical genetics
conditional
gain of function
null
reduction of function
unspecified
Large-scale survey
null
overexpression
Resources
480 total interaction(s) for 250 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 66
  • Affinity Capture-RNA: 6
  • Affinity Capture-Western: 1
  • Co-fractionation: 3
  • Co-purification: 1
  • Two-hybrid: 1

Genetic Interactions
  • Dosage Rescue: 14
  • Negative Genetic: 138
  • Phenotypic Enhancement: 4
  • Phenotypic Suppression: 1
  • Positive Genetic: 30
  • Synthetic Growth Defect: 63
  • Synthetic Lethality: 145
  • Synthetic Rescue: 7

Resources
Expression Summary
histogram
Resources
Length (a.a.) 1,876
Molecular Weight (Da) 214,849
Isoelectric Point (pI) 7.19
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXII:809997 to 815627 | ORF Map | GBrowse
SGD ORF map
Last Update Coordinates: 2004-02-05 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..5631 809997..815627 2004-02-05 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000004334
SUMMARY PARAGRAPH for FKS1

1,3-beta-D-glucan synthase (GS) is an enzymatic complex in the plasma membrane responsible for the synthesis of 1,3-beta-D-glucan, a polysaccharide that is the main structural component of the cell wall (reviewed in 7). The GS complex consists of a catalytic subunit and a regulatory subunit, both of which are essential for the complex activity (8). The regulatory subunit is a GTP-binding protein encoded by RHO1, which acts as an activator responsive to cell morphogenesis signals (9, 4, 10). FKS1 and GSC2 are believed to encode the catalytic subunit with the activity of UDP-glucose:1,3-beta-D-glucan 3-beta-glucose transferase, which catalyzes the transfer of a glucose moiety from UDP-glucose to the glucan chain (5). The two genes encode closely related integral membrane proteins that appear to act as alternate subunits with overlapping functions. FKS1 is primarily expressed during vegetative growth, whereas GSC2 is induced under starvation, during sporulation, and in response to mating pheromones (11). Null mutation of either gene is not lethal, although the fks1 null mutant shows a decrease of glucan and an increase of the chitin and mannoprotein levels in the cell wall (12) and the gsc2 null mutant shows defects in spore wall formation (13). The double null mutant fks1 gsc2 is not viable, indicating that the GS function is essential (11). The third gene, FKS3, has been identified based on sequence similarity to FKS1 and GSC2, and shown to be involved in spore wall assembly, but its exact function remains unclear (13).

The activity of glucan synthase is controlled by complex regulatory networks. The TOR signaling pathway that controls responses to nutrient availability, activates the GS regulatory subunit, Rho1p, via Tor2p regulation of the GDP/GTP exchange factor Rom2p (14). Rho1p is also known to regulate protein kinase C (Pkc1p), a component of a mitogen-activated protein kinase (MAPK) cascade that controls cell integrity (9, 15, 16). The Pkc1p cell integrity signaling pathway has been shown to be involved in cell-cycle regulated expression of FKS1 (17) and may also be required for thermal induction of GSC2 (18). In addition to Rho1p, another component of the Pkc1p cell integrity pathway, Smi1p, is required for normal levels of the GS activity (19). During spore wall assembly, the Gsc2p subunit is regulated by a sporulation-specific mitogen-activated protein kinase Smk1p (20). GSC2 expression is induced by calcium in a calcineurin-dependent manner. This observation explains the sensitivity of the fks1 ("FK506 sensitive") mutant to calcineurin inhibitors FK506 and cyclosporin A (1, 11).

Glucan synthesis is essential for cell viability and it is specific to fungi, which makes glucan synthase a useful target of antifungal drugs. Lipopeptide antifungal agents, echinocandins and pneumocandins, have been identified as inhibitors of glucan synthase and are believed to target directly the catalytic subunits of the GS complex (reviewed in 21).

Last updated: 2007-06-22 Contact SGD

References cited on this page View Complete Literature Guide for FKS1
1) Parent SA, et al.  (1993) Calcineurin-dependent growth of an FK506- and CsA-hypersensitive mutant of Saccharomyces cerevisiae. J Gen Microbiol 139(12):2973-84
2) Garrett-Engele P, et al.  (1995) Calcineurin, the Ca2+/calmodulin-dependent protein phosphatase, is essential in yeast mutants with cell integrity defects and in mutants that lack a functional vacuolar H(+)-ATPase. Mol Cell Biol 15(8):4103-14
3) Inoue SB, et al.  (1995) Characterization and gene cloning of 1,3-beta-D-glucan synthase from Saccharomyces cerevisiae. Eur J Biochem 231(3):845-54
4) Qadota H, et al.  (1996) Identification of yeast Rho1p GTPase as a regulatory subunit of 1,3-beta-glucan synthase. Science 272(5259):279-81
5) Douglas CM, et al.  (1994) The Saccharomyces cerevisiae FKS1 (ETG1) gene encodes an integral membrane protein which is a subunit of 1,3-beta-D-glucan synthase. Proc Natl Acad Sci U S A 91(26):12907-11
6) Byrne KP and Wolfe KH  (2005) The Yeast Gene Order Browser: combining curated homology and syntenic context reveals gene fate in polyploid species. Genome Res 15(10):1456-61
7) Klis FM, et al.  (2002) Dynamics of cell wall structure in Saccharomyces cerevisiae. FEMS Microbiol Rev 26(3):239-56
8) Mol PC, et al.  (1994) A GTP-binding protein regulates the activity of (1-->3)-beta-glucan synthase, an enzyme directly involved in yeast cell wall morphogenesis. J Biol Chem 269(49):31267-74
9) Drgonova J, et al.  (1996) Rho1p, a yeast protein at the interface between cell polarization and morphogenesis. Science 272(5259):277-9
10) Mazur P and Baginsky W  (1996) In vitro activity of 1,3-beta-D-glucan synthase requires the GTP-binding protein Rho1. J Biol Chem 271(24):14604-9
11) Mazur P, et al.  (1995) Differential expression and function of two homologous subunits of yeast 1,3-beta-D-glucan synthase. Mol Cell Biol 15(10):5671-81
12) Lesage G, et al.  (2004) Analysis of beta-1,3-glucan assembly in Saccharomyces cerevisiae using a synthetic interaction network and altered sensitivity to caspofungin. Genetics 167(1):35-49
13) Ishihara S, et al.  (2007) Homologous subunits of 1,3-beta-glucan synthase are important for spore wall assembly in Saccharomyces cerevisiae. Eukaryot Cell 6(2):143-56
14) Schmidt A, et al.  (1997) The yeast phosphatidylinositol kinase homolog TOR2 activates RHO1 and RHO2 via the exchange factor ROM2. Cell 88(4):531-42
15) Gustin MC, et al.  (1998) MAP kinase pathways in the yeast Saccharomyces cerevisiae. Microbiol Mol Biol Rev 62(4):1264-300
16) Heinisch JJ, et al.  (1999) The protein kinase C-mediated MAP kinase pathway involved in the maintenance of cellular integrity in Saccharomyces cerevisiae. Mol Microbiol 32(4):671-80
17) Igual JC, et al.  (1996) Coordinated regulation of gene expression by the cell cycle transcription factor Swi4 and the protein kinase C MAP kinase pathway for yeast cell integrity. EMBO J 15(18):5001-13
18) Kamada Y, et al.  (1996) Activation of yeast protein kinase C by Rho1 GTPase. J Biol Chem 271(16):9193-6
19) Martin-Yken H, et al.  (2003) The interaction of Slt2 MAP kinase with Knr4 is necessary for signalling through the cell wall integrity pathway in Saccharomyces cerevisiae. Mol Microbiol 49(1):23-35
20) Huang LS, et al.  (2005) The Smk1p MAP kinase negatively regulates Gsc2p, a 1,3-beta-glucan synthase, during spore wall morphogenesis in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 102(35):12431-6
21) Kurtz MB and Douglas CM  (1997) Lipopeptide inhibitors of fungal glucan synthase. J Med Vet Mycol 35(2):79-86