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Gene Review

GAS1  -  1,3-beta-glucanosyltransferase GAS1

Saccharomyces cerevisiae S288c

Synonyms: CWH52, GGP1, Glycolipid-anchored surface protein 1, Glycoprotein GP115, YM9952.09, ...
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Disease relevance of GAS1

  • Tobacco protoplasts were transiently transfected with a truncated form of the Clostridium thermocellum endoglucanase E reporter gene (celE') fused with a tobacco secretion signal (PR-1a) at the N-terminus and either a yeast (GAS1), mammalian (Thy-1) or putative plant (LeAGP-1) GPI-anchor addition signal at the C-terminus [1].

High impact information on GAS1

  • Emp24p and Erv25p can be directly cross-linked to Gas1p in ER-derived vesicles [2].
  • In the absence of Pma1-D378N, ER export of wild-type Pma1 is not affected by eps1 deletion, but export of the plasma membrane protein Gas1 is delayed [3].
  • Consistent with this model, the extracellular proteins Gas1p and Cts1p were localized to an internal compartment in sporulating cells [4].
  • GPI anchor attachment is required for Gas1p transport from the endoplasmic reticulum in COP II vesicles [5].
  • Cells remain competent to manufacture anchor components and to process Gas1p efficiently once inositol is restored [5].

Biological context of GAS1

  • We found that the inactivation of the GAS1 gene in the host strain led to a supersecretory phenotype yielding a considerable increase, from 8 to 55 mg/liter, in rhIGF-1 production [6].
  • The cloned GGP1 (GAS1) gene, which encodes a major GPI-anchored glycoprotein (gp115) of Saccharomyces cerevisiae of unknown function, was used to direct the inactivation of the chromosomal gene in haploid and diploid strains by gene replacement [7].
  • In order to discover whether the upregulation of chitin synthesis proceeds through the canonical transport and activation pathway of Chs3p or through an alternative one, here we studied the effects of the inactivation of the GAS1 and CHS4-5-6-7 genes [8].
  • A C. glabrata gene family, CgGAS1-3, that shares significant homologies with both the GAS1 gene of Saccharomyces cerevisiae, which is necessary for cell wall assembly, and the pH-regulated genes PHR1 and PHR2 of Candida albicans, which are involved in cell wall assembly and required for virulence, has been cloned [9].
  • The overexpression of these nonfunctional alleles in wild-type cells leads to the accumulation of the free GPI precursor lipid CP2, delays the maturation of the GPI protein Gas1p, and arrests cell growth [10].

Anatomical context of GAS1

  • The fungal GAS1-related genes encode GPI-anchored beta-1,3-glucanosyltransferase, and their loss causes a defect in the assembly of the cell wall [11].
  • We have developed a system to express this antigen in yeast as a fusion protein with the C-terminal region of the yeast membrane protein GAS1, which would render the recombinant protein anchored to the plasma membrane by a glycosylphosphatidylinositol (GPI) anchor [12].
  • Contrary to Gas1p, which is not affected by the deletion of the V-ATPase complex in the V-ATPase null mutants, the amount of Pma1p in the plasma membrane is markedly reduced, and there is a large accumulation of the protein in the endoplasmic reticulum [13].
  • We showed by immunofluorescence, sucrose-gradient analysis and quantitative Western analysis that the mutant mislocalized Emp47p to the vacuole at high temperature, while Golgi structures were apparently normal and biosynthetic routing of the vacuolar carboxypeptidase Y (CPY) and the plasma membrane GPI-anchored protein Gas1p were unaffected [14].
  • A yeast mutant that lacks Emp24p (emp24 delta) is viable, but periplasmic invertase and the glycosylphosphatidyl-inositol-anchored plasma membrane protein Gas1p are delivered to the Golgi apparatus with reduced kinetics, whereas transport of alpha-factor, acid phosphatase and two vacuolar proteins is unaffected [15].

Associations of GAS1 with chemical compounds

  • The transcription of CWH53 was cell cycle-dependent and, similar to GAS1/CWH52, increased in late G1, indicating that the formation of beta-glucan is cell cycle-regulated [16].
  • Using lipid biosynthetic mutants we could demonstrate that conditions that impair the synthesis of sphingolipids and ergosterol also disrupt raft association of Gas1p and Pma1p but not the secretion of acid phosphatase [17].
  • Interestingly, sterol structures unable to support endocytosis allowed transport of the glycosylphosphatidylinositol-anchored protein Gas1p from the endoplasmic reticulum to Golgi compartment [18].
  • In constrast to yeast, only ceramide was found in the GPI anchor structures of A. fumigatus, even for Gel1p, a homolog of Gas1p in S. cerevisiae that contains diacylglycerol [19].
  • Gas1p is organized into three modules: a catalytic domain; a cys-rich domain; and a highly O-glycosylated serine-rich region [20].

Physical interactions of GAS1


Other interactions of GAS1

  • Chitin synthase III is essential for the increase in chitin level and for cell integrity in cells lacking Gas1p, a beta(1,3)-glucanosyltransferase [8].
  • Strains deleted for GAS1, GPI7, or KNR4 release higher amounts of mannoproteins and polysaccharides to the medium [22].
  • We show that Emp24p is directly required for efficient packaging of a lumenal cargo protein, Gas1p, into ER-derived vesicles [2].
  • Correspondingly, Gas1 processing is slowed in cells bearing a deletion in YOS9 [23].
  • Disruption of GPI1 yields viable haploid cells that are temperature-sensitive for growth, for [3H]inositol incorporation into protein, and for GPI anchor-dependent processing of the Gas1/Ggp1 protein and that lack in vitro N-acetylglucosaminylphosphatidylinositol synthetic activity [24].

Analytical, diagnostic and therapeutic context of GAS1


  1. Glycosyl-phosphatidylinositol-anchor addition signals are processed in Nicotiana tabacum. Takos, A.M., Dry, I.B., Soole, K.L. Plant J. (2000) [Pubmed]
  2. The Emp24 complex recruits a specific cargo molecule into endoplasmic reticulum-derived vesicles. Muñiz, M., Nuoffer, C., Hauri, H.P., Riezman, H. J. Cell Biol. (2000) [Pubmed]
  3. Eps1, a novel PDI-related protein involved in ER quality control in yeast. Wang, Q., Chang, A. EMBO J. (1999) [Pubmed]
  4. Prospore membrane formation defines a developmentally regulated branch of the secretory pathway in yeast. Neiman, A.M. J. Cell Biol. (1998) [Pubmed]
  5. GPI anchor attachment is required for Gas1p transport from the endoplasmic reticulum in COP II vesicles. Doering, T.L., Schekman, R. EMBO J. (1996) [Pubmed]
  6. Improved secretion of native human insulin-like growth factor 1 from gas1 mutant Saccharomyces cerevisiae cells. Vai, M., Brambilla, L., Orlandi, I., Rota, N., Ranzi, B.M., Alberghina, L., Porro, D. Appl. Environ. Microbiol. (2000) [Pubmed]
  7. Physiological analysis of mutants indicates involvement of the Saccharomyces cerevisiae GPI-anchored protein gp115 in morphogenesis and cell separation. Popolo, L., Vai, M., Gatti, E., Porello, S., Bonfante, P., Balestrini, R., Alberghina, L. J. Bacteriol. (1993) [Pubmed]
  8. Maintenance of cell integrity in the gas1 mutant of Saccharomyces cerevisiae requires the Chs3p-targeting and activation pathway and involves an unusual Chs3p localization. Carotti, C., Ferrario, L., Roncero, C., Valdivieso, M.H., Duran, A., Popolo, L. Yeast (2002) [Pubmed]
  9. A GAS-like gene family in the pathogenic fungus Candida glabrata. Weig, M., Haynes, K., Rogers, T.R., Kurzai, O., Frosch, M., Mühlschlegel, F.A. Microbiology (Reading, Engl.) (2001) [Pubmed]
  10. Active site determination of Gpi8p, a caspase-related enzyme required for glycosylphosphatidylinositol anchor addition to proteins. Meyer, U., Benghezal, M., Imhof, I., Conzelmann, A. Biochemistry (2000) [Pubmed]
  11. SKG1, a suppressor gene of synthetic lethality of kex2Deltagas1Delta mutations, encodes a novel membrane protein that affects cell wall composition. Tomishige, N., Noda, Y., Adachi, H., Shimoi, H., Yoda, K. Yeast (2005) [Pubmed]
  12. Expression of Mycobacterium leprae 18-kDa antigen in yeast in a GPI-anchored form. Amorim, A.G., Cardoso-de-Almeida, M.L., Carrington, M., Morga, D.P., Riezman, H., Zerbini, L.F., Piestun, V.S., Castilho-Valavicius, B.A. Braz. J. Med. Biol. Res. (1994) [Pubmed]
  13. Altered distribution of the yeast plasma membrane H+-ATPase as a feature of vacuolar H+-ATPase null mutants. Perzov, N., Nelson, H., Nelson, N. J. Biol. Chem. (2000) [Pubmed]
  14. Yeast cys3 and gsh1 mutant cells display overlapping but non-identical symptoms of oxidative stress with regard to subcellular protein localization and CDP-DAG metabolism. Matiach, A., Schröder-Köhne, S. Mol. Genet. Genomics (2001) [Pubmed]
  15. The absence of Emp24p, a component of ER-derived COPII-coated vesicles, causes a defect in transport of selected proteins to the Golgi. Schimmöller, F., Singer-Krüger, B., Schröder, S., Krüger, U., Barlowe, C., Riezman, H. EMBO J. (1995) [Pubmed]
  16. Identification of two cell cycle regulated genes affecting the beta 1,3-glucan content of cell walls in Saccharomyces cerevisiae. Ram, A.F., Brekelmans, S.S., Oehlen, L.J., Klis, F.M. FEBS Lett. (1995) [Pubmed]
  17. Lipid rafts function in biosynthetic delivery of proteins to the cell surface in yeast. Bagnat, M., Keränen, S., Shevchenko, A., Shevchenko, A., Simons, K. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  18. Multiple functions of sterols in yeast endocytosis. Heese-Peck, A., Pichler, H., Zanolari, B., Watanabe, R., Daum, G., Riezman, H. Mol. Biol. Cell (2002) [Pubmed]
  19. Structures of the glycosylphosphatidylinositol membrane anchors from Aspergillus fumigatus membrane proteins. Fontaine, T., Magnin, T., Melhert, A., Lamont, D., Latge, J.P., Ferguson, M.A. Glycobiology (2003) [Pubmed]
  20. Characterization of recombinant forms of the yeast Gas1 protein and identification of residues essential for glucanosyltransferase activity and folding. Carotti, C., Ragni, E., Palomares, O., Fontaine, T., Tedeschi, G., Rodríguez, R., Latgé, J.P., Vai, M., Popolo, L. Eur. J. Biochem. (2004) [Pubmed]
  21. Arl1p is involved in transport of the GPI-anchored protein Gas1p from the late Golgi to the plasma membrane. Liu, Y.W., Lee, S.W., Lee, F.J. J. Cell. Sci. (2006) [Pubmed]
  22. Genetic Determinants of the Release of Mannoproteins of Enological Interest by Saccharomyces cerevisiae. Gonzalez-Ramos, D., Gonzalez, R. J. Agric. Food Chem. (2006) [Pubmed]
  23. YOS9, the putative yeast homolog of a gene amplified in osteosarcomas, is involved in the endoplasmic reticulum (ER)-Golgi transport of GPI-anchored proteins. Friedmann, E., Salzberg, Y., Weinberger, A., Shaltiel, S., Gerst, J.E. J. Biol. Chem. (2002) [Pubmed]
  24. Gpi1, a Saccharomyces cerevisiae protein that participates in the first step in glycosylphosphatidylinositol anchor synthesis. Leidich, S.D., Orlean, P. J. Biol. Chem. (1996) [Pubmed]
  25. Cloning, disruption and protein secretory phenotype of the GAS1 homologue of Pichia pastoris. Marx, H., Sauer, M., Resina, D., Vai, M., Porro, D., Valero, F., Ferrer, P., Mattanovich, D. FEMS Microbiol. Lett. (2006) [Pubmed]
  26. Three-dimensional structure of the catalytic domain of the yeast beta-(1,3)-glucan transferase Gas1: a molecular modeling investigation. Papaleo, E., Fantucci, P., Vai, M., De Gioia, L. Journal of molecular modeling (Online) (2006) [Pubmed]
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