GAP1/YKR039W Summary Help

Standard Name GAP1
Systematic Name YKR039W
Feature Type ORF, Verified
Description General amino acid permease; Gap1p senses the presence of amino acid substrates to regulate localization to the plasma membrane when needed; essential for invasive growth (1, 2, 3, 4 and see Summary Paragraph)
Name Description General Amino acid Permease
Chromosomal Location
ChrXI:515063 to 516871 | ORF Map | GBrowse
Genetic position: 27 cM
Gene Ontology Annotations All GAP1 GO evidence and references
  View Computational GO annotations for GAP1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 9 genes
Classical genetics
Large-scale survey
155 total interaction(s) for 109 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 6
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 35
  • Co-fractionation: 2
  • Co-localization: 2
  • Co-purification: 1
  • PCA: 6
  • Reconstituted Complex: 2
  • Two-hybrid: 17

Genetic Interactions
  • Dosage Growth Defect: 1
  • Dosage Rescue: 9
  • Negative Genetic: 8
  • Phenotypic Enhancement: 7
  • Phenotypic Suppression: 3
  • Positive Genetic: 12
  • Synthetic Growth Defect: 10
  • Synthetic Lethality: 33

Expression Summary
Length (a.a.) 602
Molecular Weight (Da) 65,655
Isoelectric Point (pI) 8.66
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrXI:515063 to 516871 | ORF Map | GBrowse
Genetic position: 27 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..1809 515063..516871 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 | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | TCDB | UniProtKB
Primary SGDIDS000001747

GAP1 encodes a general amino acid permease that directs uptake of all the naturally occurring L-amino acids, related compounds such as ornithine and citrulline, some D-amino acids, toxic amino acid analogs such as azetidine-2-carboxylate, and the polyamines putrescine and spermidine (5, 6, 7, 8, 9). GAP1 is regulated in response to the available nitrogen source (6). In the presence of an optimal nitrogen source, such as glutamate or glutamine, the amino acid transport activity of Gap1p is low while in the presence a poor nitrogen source, such as proline or arginine, permease activity is induced. The nitrogen-dependent regulation of GAP1 is complex, occurring both transcriptionally and post-translationally (6, 10, 11).

GAP1 is transcriptionally regulated by the available nitrogen source via nitrogen catabolite repression (NCR) (5). Under nitrogen-poor conditions, GAP1 expression is upregulated by the transcriptional activators Gln3p and Gat1p, which bind to the UASNTR sequence 5-GATAAG-3 (12). Maximum expression is dependent on the presence of the co-activator Hfi1p, which has been suggested to recruit the Ada2/Gcn5/Ada3 transcriptional activation complex to Gln3p and Gat1p (13). Conversely, in nitrogen-rich media, GAP1 transcription is repressed by sequestration of Gln3p and Gat1p to the cytosol by the transcription factor Ure2p (6, 14). GAP1 expression is also directly downregulated by the NCR-mediating transcriptional repressors Dal80p and Gzf3p, which compete with Gln3p and Gat1p for the UASNTR binding site (15, 16).

The quality of the nitrogen source also affects Gap1p activity by regulating permease localization and degradation (10, 11). In the absence of an optimal nitrogen source, Gap1p is transported to the plasma membrane via COPII-coated vesicles (17). Vesicle packaging and cell-surface delivery has been shown to be dependent on the COPII complex component Sec13p, the chaperone protein Shr3p, and Lst4p, Lst7p, Lst8p, and Npr1p (18, 19, 20). Npr1p also contributes to Gap1p stability and retention at the plasma membrane (20). Upon addition of a preferred nitrogen source, any Gap1p already present at the cell surface is rapidly poly-ubiquitinated, a process requiring the ubiquitin ligase Rsp5p and the Rsp5p-associated proteins Bul1p and Bul2p (21, 22), leading to Gap1p endocytosis 11). This is followed by permease deubiquitination and incorporation into late-endosome multivesicular bodies, mediated by the ubiquitin hydrolase Doa4p and the class E vacuolar sorting factor Bro1p (23, 24), and ultimately results in the sorting of Gap1p to the vacuole for degradation 11). The presence of preferred nitrogen sources also directs the ubiquitination and trafficking of newly-synthesized Gap1p with the permease bypassing the cell surface and being sorted directly from the Golgi to the vacuole, a process facilitated by Gga1p, Gga2p and the t-SNARE Pep12p (10, 25, 24). In addition to ubiquitination, Gap1p sorting and stability also has been suggested to depend on its phosphorylation state; phosphorylation is correlated with permease activity and dephosphorylation with lack of activity (6).

Last updated: 2005-10-24 Contact SGD

References cited on this page View Complete Literature Guide for GAP1
1) Magasanik B and Kaiser CA  (2002) Nitrogen regulation in Saccharomyces cerevisiae. Gene 290(1-2):1-18
2) Chen EJ and Kaiser CA  (2002) Amino acids regulate the intracellular trafficking of the general amino acid permease of Saccharomycescerevisiae. Proc Natl Acad Sci U S A 99(23):14837-42
3) Cain NE and Kaiser CA  (2011) Transport activity-dependent intracellular sorting of the yeast general amino acid permease. Mol Biol Cell 22(11):1919-29
4) Torbensen R, et al.  (2012) Amino Acid Transporter Genes Are Essential for FLO11-Dependent and FLO11-Independent Biofilm Formation and Invasive Growth in Saccharomyces cerevisiae. PLoS One 7(7):e41272
5) Jauniaux JC and Grenson M  (1990) GAP1, the general amino acid permease gene of Saccharomyces cerevisiae. Nucleotide sequence, protein similarity with the other bakers yeast amino acid permeases, and nitrogen catabolite repression. Eur J Biochem 190(1):39-44
6) Stanbrough M and Magasanik B  (1995) Transcriptional and posttranslational regulation of the general amino acid permease of Saccharomyces cerevisiae. J Bacteriol 177(1):94-102
7) Regenberg B and Hansen J  (2000) GAP1, a novel selection and counter-selection marker for multiple gene disruptions in Saccharomyces cerevisiae. Yeast 16(12):1111-9
8) Andreasson C, et al.  (2004) Four permeases import proline and the toxic proline analogue azetidine-2-carboxylate into yeast. Yeast 21(3):193-9
9) Uemura T, et al.  (2005) Uptake of putrescine and spermidine by Gap1p on the plasma membrane in Saccharomyces cerevisiae. Biochem Biophys Res Commun 328(4):1028-33
10) Roberg KJ, et al.  (1997) Physiological regulation of membrane protein sorting late in the secretory pathway of Saccharomyces cerevisiae. J Cell Biol 137(7):1469-82
11) Springael JY and Andre B  (1998) Nitrogen-regulated ubiquitination of the Gap1 permease of Saccharomyces cerevisiae. Mol Biol Cell 9(6):1253-63
12) Stanbrough M and Magasanik B  (1996) Two transcription factors, Gln3p and Nil1p, use the same GATAAG sites to activate the expression of GAP1 of Saccharomyces cerevisiae. J Bacteriol 178(8):2465-8
13) Soussi-Boudekou S and Andre B  (1999) A co-activator of nitrogen-regulated transcription in Saccharomyces cerevisiae. Mol Microbiol 31(3):753-62
14) Kulkarni AA, et al.  (2001) Gln3p nuclear localization and interaction with Ure2p in Saccharomyces cerevisiae. J Biol Chem 276(34):32136-44
15) Rowen DW, et al.  (1997) Role of GATA factor Nil2p in nitrogen regulation of gene expression in Saccharomyces cerevisiae. J Bacteriol 179(11):3761-6
16) Coffman JA, et al.  (1997) Cross regulation of four GATA factors that control nitrogen catabolic gene expression in Saccharomyces cerevisiae. J Bacteriol 179(11):3416-29
17) Malkus P, et al.  (2002) Concentrative sorting of secretory cargo proteins into COPII-coated vesicles. J Cell Biol 159(6):915-21
18) Gilstring CF, et al.  (1999) Shr3p mediates specific COPII coatomer-cargo interactions required for the packaging of amino acid permeases into ER-derived transport vesicles. Mol Biol Cell 10(11):3549-65
19) Roberg KJ, et al.  (1997) Control of amino acid permease sorting in the late secretory pathway of Saccharomyces cerevisiae by SEC13, LST4, LST7 and LST8. Genetics 147(4):1569-84
20) De Craene JO, et al.  (2001) The Npr1 kinase controls biosynthetic and endocytic sorting of the yeast Gap1 permease. J Biol Chem 276(47):43939-48
21) Soetens O, et al.  (2001) Ubiquitin is required for sorting to the vacuole of the yeast general amino acid permease, Gap1. J Biol Chem 276(47):43949-57
22) Helliwell SB, et al.  (2001) Components of a ubiquitin ligase complex specify polyubiquitination and intracellular trafficking of the general amino acid permease. J Cell Biol 153(4):649-62
23) Springael JY, et al.  (1999) NH4+-induced down-regulation of the Saccharomyces cerevisiae Gap1p permease involves its ubiquitination with lysine-63-linked chains. J Cell Sci 112 ( Pt 9)():1375-83
24) Nikko E, et al.  (2003) Permease recycling and ubiquitination status reveal a particular role for Bro1 in the multivesicular body pathway. J Biol Chem 278(50):50732-43
25) Scott PM, et al.  (2004) GGA proteins bind ubiquitin to facilitate sorting at the trans-Golgi network. Nat Cell Biol 6(3):252-9