Gene Symbol: GAP1
Description: amino acid permease GAP1
Alias: amino acid permease GAP1
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Springael J, Andre B. Nitrogen-regulated ubiquitination of the Gap1 permease of Saccharomyces cerevisiae. Mol Biol Cell. 1998;9:1253-63 pubmed
    ..growing on proline as the sole nitrogen source induces rapid inactivation and degradation of the general amino acid permease Gap1 through a process requiring the Npi1/Rsp5 ubiquitin (Ub) ligase...
  2. Iraqui I, Vissers S, Bernard F, De Craene J, Boles E, Urrestarazu A, et al. Amino acid signaling in Saccharomyces cerevisiae: a permease-like sensor of external amino acids and F-Box protein Grr1p are required for transcriptional induction of the AGP1 gene, which encodes a broad-specificity amino acid permease. Mol Cell Biol. 1999;19:989-1001 pubmed
    ..The essential role of Grr1p in this amino acid signaling pathway lends further support to the hypothesis that this protein participates in integrating nutrient availability with the cell cycle. ..
  3. Risinger A, Kaiser C. Different ubiquitin signals act at the Golgi and plasma membrane to direct GAP1 trafficking. Mol Biol Cell. 2008;19:2962-72 pubmed publisher
  4. Nikko E, Marini A, Andre B. Permease recycling and ubiquitination status reveal a particular role for Bro1 in the multivesicular body pathway. J Biol Chem. 2003;278:50732-43 pubmed
    Ubiquitination of the yeast Gap1 permease at the plasma membrane triggers its endocytosis followed by targeting to the vacuolar lumen for degradation. We previously identified Bro1 as a protein essential to this down-regulation...
  5. Risinger A, Cain N, Chen E, Kaiser C. Activity-dependent reversible inactivation of the general amino acid permease. Mol Biol Cell. 2006;17:4411-9 pubmed
    ..Exploiting this toxicity, we isolated gap1 alleles deficient in transport of a subset of amino acids...
  6. Van Zeebroeck G, Bonini B, Versele M, Thevelein J. Transport and signaling via the amino acid binding site of the yeast Gap1 amino acid transceptor. Nat Chem Biol. 2009;5:45-52 pubmed publisher
    ..We have screened 319 amino acid analogs to identify compounds that act on Gap1, a transporting amino acid transceptor in yeast that triggers activation of the protein kinase A pathway...
  7. Gilstring C, Melin Larsson M, Ljungdahl P. Shr3p mediates specific COPII coatomer-cargo interactions required for the packaging of amino acid permeases into ER-derived transport vesicles. Mol Biol Cell. 1999;10:3549-65 pubmed
  8. Cain N, Kaiser C. Transport activity-dependent intracellular sorting of the yeast general amino acid permease. Mol Biol Cell. 2011;22:1919-29 pubmed publisher
    ..These results indicate a parsimonious regulatory mechanism by which Gap1p senses its transport substrates to set an appropriate level of transporter activity at the cell surface. ..
  9. Roberg K, Rowley N, Kaiser C. Physiological regulation of membrane protein sorting late in the secretory pathway of Saccharomyces cerevisiae. J Cell Biol. 1997;137:1469-82 pubmed
    ..Together, these studies demonstrate that both a nitrogen-sensing mechanism and Sec13p control Gap1p transport from the Golgi to the plasma membrane. ..

More Information


  1. Lauwers E, Grossmann G, Andre B. Evidence for coupled biogenesis of yeast Gap1 permease and sphingolipids: essential role in transport activity and normal control by ubiquitination. Mol Biol Cell. 2007;18:3068-80 pubmed
    ..We show here that the yeast general amino acid permease Gap1 synthesized in the absence of sphingolipid (SL) biosynthesis is delivered to the cell surface but ..
  2. Rubio Texeira M, Kaiser C. Amino acids regulate retrieval of the yeast general amino acid permease from the vacuolar targeting pathway. Mol Biol Cell. 2006;17:3031-50 pubmed
    ..Thus the role of ubiquitination appears to be a signal for delivery of Gap1p to the MVE, whereas amino acid abundance appears to control the cycling of Gap1p from the MVE to the plasma membrane. ..
  3. Gresham D, Usaite R, Germann S, Lisby M, Botstein D, Regenberg B. Adaptation to diverse nitrogen-limited environments by deletion or extrachromosomal element formation of the GAP1 locus. Proc Natl Acad Sci U S A. 2010;107:18551-6 pubmed publisher
    ..identify copy-number variation associated with adaptation and observed frequent amplifications and deletions at the GAP1 locus. GAP1 encodes the general amino acid permease, which transports amino acids across the plasma membrane...
  4. Kuehn M, Herrmann J, Schekman R. COPII-cargo interactions direct protein sorting into ER-derived transport vesicles. Nature. 1998;391:187-90 pubmed
    ..Our results indicate that cargo packaging signals and soluble cargo adaptors are recognized by a recruitment complex comprising Sar1-GTP and Sec23/24...
  5. Malkus P, Jiang F, Schekman R. Concentrative sorting of secretory cargo proteins into COPII-coated vesicles. J Cell Biol. 2002;159:915-21 pubmed
    ..Mutation of a diacidic sequence present in the COOH-terminal cytosolic domain of Gap1p eliminated concentrative sorting of this protein. ..
  6. Helliwell S, Losko S, Kaiser C. Components of a ubiquitin ligase complex specify polyubiquitination and intracellular trafficking of the general amino acid permease. J Cell Biol. 2001;153:649-62 pubmed
    ..These results indicate that Bul1p and Bul2p, together with Rsp5p, generate a polyubiquitin signal on Gap1p that specifies its intracellular targeting to the vacuole. ..
  7. Andréasson C, Neve E, Ljungdahl P. Four permeases import proline and the toxic proline analogue azetidine-2-carboxylate into yeast. Yeast. 2004;21:193-9 pubmed
    ..Saccharomyces cerevisiae cells by four amino acid permeases, including two nitrogen-regulated permeases (PUT4 and GAP1) and two permeases that are regulated by the SPS sensor of extracellular amino acids (AGP1 and GNP1)...
  8. Merhi A, Andre B. Internal amino acids promote Gap1 permease ubiquitylation via TORC1/Npr1/14-3-3-dependent control of the Bul arrestin-like adaptors. Mol Cell Biol. 2012;32:4510-22 pubmed publisher
    ..The yeast general amino acid permease, Gap1, is ubiquitylated and downregulated when a good nitrogen source like ammonium is provided to cells growing on a ..
  9. Scott P, Bilodeau P, Zhdankina O, Winistorfer S, Hauglund M, Allaman M, et al. GGA proteins bind ubiquitin to facilitate sorting at the trans-Golgi network. Nat Cell Biol. 2004;6:252-9 pubmed
    ..their GAT domain and demonstrate that this interaction is required for the ubiquitin-dependent sorting of the Gap1 amino acid transporter from the TGN to endosomes...
  10. Lauwers E, Jacob C, Andre B. K63-linked ubiquitin chains as a specific signal for protein sorting into the multivesicular body pathway. J Cell Biol. 2009;185:493-502 pubmed publisher
    ..In this study, we show that K63-linked ubiquitylation of the Gap1 permease is essential for its entry into the MVB pathway...
  11. O Donnell A, Apffel A, Gardner R, Cyert M. Alpha-arrestins Aly1 and Aly2 regulate intracellular trafficking in response to nutrient signaling. Mol Biol Cell. 2010;21:3552-66 pubmed publisher
    ..In contrast, we show that yeast ?-arrestins, Aly1 and Aly2, control intracellular sorting of Gap1, the general amino acid permease, in response to nutrients...
  12. ter Schure E, Silljé H, Vermeulen E, Kalhorn J, Verkleij A, Boonstra J, et al. Repression of nitrogen catabolic genes by ammonia and glutamine in nitrogen-limited continuous cultures of Saccharomyces cerevisiae. Microbiology. 1998;144 ( Pt 5):1451-62 pubmed
    ..To discriminate between ammonia- and glutamine-driven repression of GAP1, PUT4, GDH1 and GLN1, a gln1-37 mutant was used. This mutant is not able to convert ammonia into glutamine...
  13. Binda M, Péli Gulli M, Bonfils G, Panchaud N, Urban J, Sturgill T, et al. The Vam6 GEF controls TORC1 by activating the EGO complex. Mol Cell. 2009;35:563-73 pubmed publisher
    ..Thus, in addition to its regulatory role in homotypic vacuolar fusion and vacuole protein sorting within the HOPS complex, Vam6 also controls TORC1 function by activating the Gtr1 subunit of the EGO complex. ..
  14. Torbensen R, Møller H, Gresham D, Alizadeh S, Ochmann D, Boles E, et al. Amino acid transporter genes are essential for FLO11-dependent and FLO11-independent biofilm formation and invasive growth in Saccharomyces cerevisiae. PLoS ONE. 2012;7:e41272 pubmed publisher
    ..Secondly, the amino acid transporter gene GAP1 was found to influence invasive growth through FLO11 as well as other FLO genes...
  15. Devasahayam G, Ritz D, Helliwell S, Burke D, Sturgill T. Pmr1, a Golgi Ca2+/Mn2+-ATPase, is a regulator of the target of rapamycin (TOR) signaling pathway in yeast. Proc Natl Acad Sci U S A. 2006;103:17840-5 pubmed
    ..Nuclear translocation of Gln-3 and Gln-3 reporter activity in pmr1 cells are impaired, but expression of functional Gap1 in the plasma membrane of a pmr1 strain in response to nitrogen limitation is enhanced...
  16. Gao M, Kaiser C. A conserved GTPase-containing complex is required for intracellular sorting of the general amino-acid permease in yeast. Nat Cell Biol. 2006;8:657-67 pubmed
    ..Together, these studies provide evidence that the GSE complex has a key role in trafficking Gap1p out of the endosome and may serve as coat proteins in this process. ..
  17. Abdel Sater F, Iraqui I, Urrestarazu A, Andre B. The external amino acid signaling pathway promotes activation of Stp1 and Uga35/Dal81 transcription factors for induction of the AGP1 gene in Saccharomyces cerevisiae. Genetics. 2004;166:1727-39 pubmed
    ..Finally, the data show that the TOR pathway mediating global nitrogen control of transcription does not interfere with the external amino acid signaling pathway. ..
  18. Morsomme P, Prescianotto Baschong C, Riezman H. The ER v-SNAREs are required for GPI-anchored protein sorting from other secretory proteins upon exit from the ER. J Cell Biol. 2003;162:403-12 pubmed
    ..Therefore, we propose that v-SNAREs are part of the cargo protein sorting machinery upon exit from the ER and that a correct sorting process is necessary for proper maturation of GPI-anchored proteins. ..
  19. Sasaki T, Takagi H. Phosphorylation of a conserved Thr357 in yeast Nedd4-like ubiquitin ligase Rsp5 is involved in down-regulation of the general amino acid permease Gap1. Genes Cells. 2013;18:459-75 pubmed publisher
    ..Rsp5 triggers the ubiquitination-dependent endocytosis of the general amino acid permease Gap1 in response to a good nitrogen source...
  20. Uemura T, Kashiwagi K, Igarashi K. Uptake of putrescine and spermidine by Gap1p on the plasma membrane in Saccharomyces cerevisiae. Biochem Biophys Res Commun. 2005;328:1028-33 pubmed
    ..Furthermore, when yeast was transformed with the GAP1 gene and cultured in the presence of 60 mM putrescine, cell growth was inhibited through overaccumulation of ..
  21. Van Zeebroeck G, Rubio Texeira M, Schothorst J, Thevelein J. Specific analogues uncouple transport, signalling, oligo-ubiquitination and endocytosis in the yeast Gap1 amino acid transceptor. Mol Microbiol. 2014;93:213-33 pubmed publisher
    The Saccharomyces cerevisiae amino acid transceptor Gap1 functions as receptor for signalling to the PKA pathway and concomitantly undergoes substrate-induced oligo-ubiquitination and endocytosis...
  22. Bernard F, Andre B. Genetic analysis of the signalling pathway activated by external amino acids in Saccharomyces cerevisiae. Mol Microbiol. 2001;41:489-502 pubmed
  23. Darvishi E, Omidi M, Bushehri A, Golshani A, Smith M. The antifungal eugenol perturbs dual aromatic and branched-chain amino acid permeases in the cytoplasmic membrane of yeast. PLoS ONE. 2013;8:e76028 pubmed publisher
    ..Finally, this study provides further evidence of the usefulness of the yeast Gene Deletion Array approach in uncovering the mode of action of natural health products. ..
  24. Stella C, Korch C, Ramos E, Bauer A, Kölling R, Mattoon J. The Saccharomyces cerevisiae LEP1/SAC3 gene is associated with leucine transport. Mol Gen Genet. 1999;262:332-41 pubmed
    ..cerevisiae is mediated by three transport systems, the general amino acid transport system (GAP), encoded by GAP1, and two group-specific systems (S1 and S2), which also transport isoleucine and valine...
  25. Grenson M, Acheroy B. Mutations affecting the activity and the regulation of the general amino-acid permease of Saccharomyces cerevisiae. Localisation of the cis-acting dominant pgr regulatory mutation in the structural gene of this permease. Mol Gen Genet. 1982;188:261-5 pubmed
    Mutants lacking the general amino acid permease activity fall into two classes of complementation. Mutations at the GAP1 locus abolish the general amino acid permease activity specifically, while those in the NPR1 locus simultaneously ..
  26. Shiga T, Yoshida N, Shimizu Y, Suzuki E, Sasaki T, Watanabe D, et al. Quality control of plasma membrane proteins by Saccharomyces cerevisiae Nedd4-like ubiquitin ligase Rsp5p under environmental stress conditions. Eukaryot Cell. 2014;13:1191-9 pubmed publisher
    ..Our findings suggest that stress-induced quality control is a common process requiring Rsp5p for plasma membrane proteins in yeast. ..
  27. Sáenz D, Chianelli M, Stella C. L-Phenylalanine Transport in Saccharomyces cerevisiae: Participation of GAP1, BAP2, and AGP1. J Amino Acids. 2014;2014:283962 pubmed publisher
    We focused on the participation of GAP1, BAP2, and AGP1 in L-phenylalanine transport in yeast...
  28. Popov Celeketic D, Bianchi F, Ruiz S, Meutiawati F, Poolman B. A Plasma Membrane Association Module in Yeast Amino Acid Transporters. J Biol Chem. 2016;291:16024-37 pubmed publisher
    ..Using in silico analyses and mutational studies we found that the C-terminal sequences of Gap1, Bap2, Hip1, Tat1, Tat2, Mmp1, Sam3, Agp1, and Gnp1 are about 50 residues long, associate with the PM, and have ..
  29. Hatakeyama R, Kamiya M, Takahara T, Maeda T. Endocytosis of the aspartic acid/glutamic acid transporter Dip5 is triggered by substrate-dependent recruitment of the Rsp5 ubiquitin ligase via the arrestin-like protein Aly2. Mol Cell Biol. 2010;30:5598-607 pubmed publisher
    ..Importantly, the interaction between Aly2 and Dip5 is accelerated in response to elevated aspartic acid availability. This result indicates that the regulation of Dip5 endocytosis is accomplished by dynamic recruitment of Rsp5 via Aly2. ..
  30. Merhi A, Gérard N, Lauwers E, Prevost M, Andre B. Systematic mutational analysis of the intracellular regions of yeast Gap1 permease. PLoS ONE. 2011;6:e18457 pubmed publisher
    The yeast general amino acid permease Gap1 is a convenient model for studying the intracellular trafficking of membrane proteins...
  31. Wielemans K, Jean C, Vissers S, Andre B. Amino acid signaling in yeast: post-genome duplication divergence of the Stp1 and Stp2 transcription factors. J Biol Chem. 2010;285:855-65 pubmed publisher
  32. Kota J, Ljungdahl P. Specialized membrane-localized chaperones prevent aggregation of polytopic proteins in the ER. J Cell Biol. 2005;168:79-88 pubmed
  33. Ghaddar K, Merhi A, Saliba E, Krammer E, Prévost M, André B. Substrate-induced ubiquitylation and endocytosis of yeast amino acid permeases. Mol Cell Biol. 2014;34:4447-63 pubmed publisher
    ..We report here that two amino acid transporters of Saccharomyces cerevisiae, the general amino acid permease (Gap1) and the arginine-specific permease (Can1), undergo ubiquitin-dependent downregulation in response to their ..
  34. Garrett J. Amino acid transport through the Saccharomyces cerevisiae Gap1 permease is controlled by the Ras/cAMP pathway. Int J Biochem Cell Biol. 2008;40:496-502 pubmed
    ..This regulation is through a post-transcriptional mechanism; transcription of GAP1 is not affected by cAMP level...
  35. Bernard F, Andre B. Ubiquitin and the SCF(Grr1) ubiquitin ligase complex are involved in the signalling pathway activated by external amino acids in Saccharomyces cerevisiae. FEBS Lett. 2001;496:81-5 pubmed
    ..This suggests that transduction to these genes of the amino acid signal generated by Ssy1 involves an SCF(Grr1)-catalysed ubiquitination step. ..
  36. Liu Z, Sekito T, Epstein C, Butow R. RTG-dependent mitochondria to nucleus signaling is negatively regulated by the seven WD-repeat protein Lst8p. EMBO J. 2001;20:7209-19 pubmed
    ..These data, together with genome-wide transcription profiling, reveal pathways regulated by glutamate, and provide insight into the regulation of cellular responses to mitochondrial dysfunction. ..
  37. Crapeau M, Merhi A, Andre B. Stress conditions promote yeast Gap1 permease ubiquitylation and down-regulation via the arrestin-like Bul and Aly proteins. J Biol Chem. 2014;289:22103-16 pubmed publisher
    b>Gap1, the yeast general amino acid permease, is a convenient model for studying how the intracellular traffic of membrane transporters is regulated...
  38. Zhang P, Du G, Zou H, Chen J, Xie G, Shi Z, et al. Effects of three permeases on arginine utilization in Saccharomyces cerevisiae. Sci Rep. 2016;6:20910 pubmed publisher
    ..The three amino acid permeases were also individually overexpressed in wild-type (WT), Δalp1Δgap1Δcan1 and Δnpr1 strains...
  39. Surma M, Klose C, Klemm R, Ejsing C, Simons K. Generic sorting of raft lipids into secretory vesicles in yeast. Traffic. 2011;12:1139-47 pubmed publisher
    ..populations of secretory vesicles isolated using natural yeast plasma membrane (PM) proteins: Pma1p, Mid2p and Gap1*p as baits...
  40. Iraqui I, Vissers S, Andre B, Urrestarazu A. Transcriptional induction by aromatic amino acids in Saccharomyces cerevisiae. Mol Cell Biol. 1999;19:3360-71 pubmed
    ..Finally, we show that Gap1p, the general amino acid permease, and Wap1p (Ycl025p), a newly discovered inducible amino acid permease with broad specificity, are the main aromatic amino acid transporters for catabolic purposes. ..