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Gene Review

YPT1  -  Rab family GTPase YPT1

Saccharomyces cerevisiae S288c

Synonyms: GTP-binding protein YPT1, Protein YP2, Rab GTPase YPT1, Transport GTPase YPT1, YFL038C, ...
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Disease relevance of YPT1

  • Here we report the identification of a gene in S. cerevisiae which codes for a 206 amino acid protein (YP2) that exhibits striking homology to the p21 products of the human c-has/bas proto-oncogenes and the transforming p21 proteins of the Harvey (v-rasH) and Kirsten (v-rasK) murine sarcoma viral oncogenes [1].
  • The protein product of the Piypt1 gene, expressed in Escherichia coli, cross-reacts with antiserum against yeast Ypt1 protein and binds GTP [2].

High impact information on YPT1

  • Our results identify Sec9 as the yeast cognate of SNAP-25 and suggest that SNARE complexes acting at specific stages of vesicular transport serve as the ultimate targets of regulation by members of the Sec4/Ypt1/Rab family of GTPases [3].
  • A set of 11 clones encoding putative GTP binding proteins highly homologous to the yeast YPT1/SEC4 gene products have been isolated from an MDCK cell cDNA library [4].
  • The loss of YPT1 function, studied in cells with the YPT1 gene on chromosome VI regulated by the galactose-inducible GAL10 promoter, led to arrested cells that were multibudded and exhibited a complete disorganization of microtubules and an apparent loss of nuclear integrity [5].
  • The 23.5 kd protein product of the ras-related YPT1 gene of S. cerevisiae was found to be essential for cell growth [5].
  • The ras-related YPT1 gene product in yeast: a GTP-binding protein that might be involved in microtubule organization [5].

Biological context of YPT1

  • The temperature-sensitive phenotype of sec35-1 is efficiently suppressed by YPT1, which encodes the rab-like GTPase required early in the secretory pathway, or by SLY1-20, which encodes a dominant form of the ER to Golgi target -SNARE-associated protein Sly1p [6].
  • The mutant cells died without exhibiting classical cell-cycle-specific arrest; nevertheless, examination of cellular DNA content suggests that the YPT1 function is required, particularly after S phase [7].
  • The YPT1 gene is thus involved in nutritional regulation of the cell cycle as well as in normal progression through the mitotic cell cycle [7].
  • In Saccharomyces cerevisiae, the GTP-binding Ypt1 protein (Ypt1p) is essential for endoplasmic reticulum-to-Golgi protein transport [8].
  • Using as hybridization probe cloned yeast YPT1 gene sequences, we have isolated from cDNA libraries prepared from RNA of mouse F9 and C3H10T1/2 cells several overlapping cDNA clones with identical sequence in the regions of overlap [9].

Anatomical context of YPT1


Associations of YPT1 with chemical compounds

  • YPT1 gene mutations were generated that either led to substitutions by serine or the deletion of one or both C-terminal cysteines [14].
  • The extension by three residues, -Val-Leu-Ser, generating a ras-typical C-terminal end, did not interfere with the mutant YPT1 protein's function although it resulted in a reduced labelling with palmitic acid [14].
  • Differential modulation of yeast actin, tubulin, and YPT1 mRNA levels by cycloheximide [15].
  • The temperature-sensitive phenotype of sec34-2 is suppressed by the rab GTPase Ypt1p that functions early in the secretory pathway, or by the dominant form of the ER to Golgi complex target-SNARE (soluble N-ethylmaleimide sensitive fusion protein attachment protein receptor)-associated protein Sly1p, Sly1-20p [16].
  • Amino acid sequences typical for guanine nucleotide-binding proteins and characteristic for ypt proteins are perfectly conserved in the mouse ypt1 protein [9].

Physical interactions of YPT1


Regulatory relationships of YPT1

  • Here we show that overexpression of YPT1 suppresses the growth and secretion defects of a ypt6 temperature-sensitive (ts) strain [19].
  • The cold-sensitive lethality that results from deleting SEC35 is suppressed by YPT1 or SLY1-20 [6].
  • Here we characterize an antiserum directed against Mrs6p and show that it specifically inhibits the geranylation of the YPT1 protein in an in vitro assay [20].
  • The SEC3 gene in high copy suppresses pfy1-111 and sec5-24 and causes synthetic growth defects with ypt1, sec8-9, sec10-2, and sec15-1 [21].
  • The mouse ypt1 protein with 71% of identical residues compared with the yeast Ypt1 protein could functionally fully replace its yeast homologue as long as the mouse gene was overexpressed under transcriptional control of the inducible GAL10 promoter [22].

Other interactions of YPT1

  • The genes SEC4 and YPT1 encode Ras-related GTP-binding proteins in the yeast Saccharomyces cerevisiae [11].
  • The ypt31/ 32 mutant secretory defect is clearly downstream from that displayed by a ypt1 mutant and is similar to that of sec4 mutant cells [23].
  • In addition, overexpression of the small GTP-binding protein Ypt1p, or of a gain if function mutant (SLY1-20) of the t-SNARE associated protein Sly1p, also confers temperature resistance [24].
  • The Rab GTPase Ypt1p and the large homodimer Uso1p are both required for tethering endoplasmic reticulum-derived vesicles to early Golgi compartments in yeast [25].
  • Genetic interaction between YPT6 and YPT1 in Saccharomyces cerevisiae [19].

Analytical, diagnostic and therapeutic context of YPT1

  • We report the cloning and sequence analysis of the yeast BAF1 gene which encodes an abundant protein previously shown to act as a transcription activator in the YPT1-TUB2 intergene region [26].
  • Immunofluorescence localization studies using affinity-purified antibody directed against the YPT1 protein showed punctate staining of the cytoplasm of growing yeast cells and very intense staining of small buds, where membrane growth and secretion are most active [27].
  • Using site-directed mutagenesis, the ras-related and essential yeast YPT1 gene was changed to generate proteins with amino acid exchanges within conserved regions [28].
  • Surprisingly, a strain with ypt1-Q67L as the only YPT1 gene in the cell has no observable growth phenotypes at temperatures ranging from 14 to 37 degrees C. In addition, these mutant cells exhibit normal rates of secretion and normal membrane morphology as determined by electron microscopy [29].
  • One chromosomal YPT1 allele in C. albicans CAI4 was readily disrupted by homologous gene targeting, but attempts to disrupt the second allele yielded no viable null mutants [30].


  1. A yeast gene encoding a protein homologous to the human c-has/bas proto-oncogene product. Gallwitz, D., Donath, C., Sander, C. Nature (1983) [Pubmed]
  2. Characterization of a Phytophthora infestans gene involved in vesicle transport. Chen, Y., Roxby, R. Gene (1996) [Pubmed]
  3. Sec9 is a SNAP-25-like component of a yeast SNARE complex that may be the effector of Sec4 function in exocytosis. Brennwald, P., Kearns, B., Champion, K., Keränen, S., Bankaitis, V., Novick, P. Cell (1994) [Pubmed]
  4. Localization of low molecular weight GTP binding proteins to exocytic and endocytic compartments. Chavrier, P., Parton, R.G., Hauri, H.P., Simons, K., Zerial, M. Cell (1990) [Pubmed]
  5. The ras-related YPT1 gene product in yeast: a GTP-binding protein that might be involved in microtubule organization. Schmitt, H.D., Wagner, P., Pfaff, E., Gallwitz, D. Cell (1986) [Pubmed]
  6. Sec35p, a novel peripheral membrane protein, is required for ER to Golgi vesicle docking. VanRheenen, S.M., Cao, X., Lupashin, V.V., Barlowe, C., Waters, M.G. J. Cell Biol. (1998) [Pubmed]
  7. The ras-like yeast YPT1 gene is itself essential for growth, sporulation, and starvation response. Segev, N., Botstein, D. Mol. Cell. Biol. (1987) [Pubmed]
  8. Identification and structure of four yeast genes (SLY) that are able to suppress the functional loss of YPT1, a member of the RAS superfamily. Dascher, C., Ossig, R., Gallwitz, D., Schmitt, H.D. Mol. Cell. Biol. (1991) [Pubmed]
  9. The ras-related ypt protein is an ubiquitous eukaryotic protein: isolation and sequence analysis of mouse cDNA clones highly homologous to the yeast YPT1 gene. Haubruck, H., Disela, C., Wagner, P., Gallwitz, D. EMBO J. (1987) [Pubmed]
  10. Molecular cloning of YPT1/SEC4-related cDNAs from an epithelial cell line. Chavrier, P., Vingron, M., Sander, C., Simons, K., Zerial, M. Mol. Cell. Biol. (1990) [Pubmed]
  11. Interactions of three domains distinguishing the Ras-related GTP-binding proteins Ypt1 and Sec4. Brennwald, P., Novick, P. Nature (1993) [Pubmed]
  12. The ER v-SNAREs are required for GPI-anchored protein sorting from other secretory proteins upon exit from the ER. Morsomme, P., Prescianotto-Baschong, C., Riezman, H. J. Cell Biol. (2003) [Pubmed]
  13. Dependence of Ypt1 and Sec4 membrane attachment on Bet2. Rossi, G., Yu, J.A., Newman, A.P., Ferro-Novick, S. Nature (1991) [Pubmed]
  14. A carboxyl-terminal cysteine residue is required for palmitic acid binding and biological activity of the ras-related yeast YPT1 protein. Molenaar, C.M., Prange, R., Gallwitz, D. EMBO J. (1988) [Pubmed]
  15. Differential modulation of yeast actin, tubulin, and YPT1 mRNA levels by cycloheximide. Munholland, J.M., Wildeman, A.G. Gene (1991) [Pubmed]
  16. Sec34p, a protein required for vesicle tethering to the yeast Golgi apparatus, is in a complex with Sec35p. VanRheenen, S.M., Cao, X., Sapperstein, S.K., Chiang, E.C., Lupashin, V.V., Barlowe, C., Waters, M.G. J. Cell Biol. (1999) [Pubmed]
  17. Structure of Rab GDP-dissociation inhibitor in complex with prenylated YPT1 GTPase. Rak, A., Pylypenko, O., Durek, T., Watzke, A., Kushnir, S., Brunsveld, L., Waldmann, H., Goody, R.S., Alexandrov, K. Science (2003) [Pubmed]
  18. Saccharomyces cerevisiae Rab-GDI displacement factor ortholog Yip3p forms distinct complexes with the Ypt1 Rab GTPase and the reticulon Rtn1p. Geng, J., Shin, M.E., Gilbert, P.M., Collins, R.N., Burd, C.G. Eukaryotic Cell (2005) [Pubmed]
  19. Genetic interaction between YPT6 and YPT1 in Saccharomyces cerevisiae. Li, B., Warner, J.R. Yeast (1998) [Pubmed]
  20. Mrs6p, the yeast homologue of the mammalian choroideraemia protein: immunological evidence for its function as the Ypt1p Rab escort protein. Benito-Moreno, R.M., Miaczynska, M., Bauer, B.E., Schweyen, R.J., Ragnini, A. Curr. Genet. (1994) [Pubmed]
  21. Sec3p is involved in secretion and morphogenesis in Saccharomyces cerevisiae. Finger, F.P., Novick, P. Mol. Biol. Cell (1997) [Pubmed]
  22. The ras-related mouse ypt1 protein can functionally replace the YPT1 gene product in yeast. Haubruck, H., Prange, R., Vorgias, C., Gallwitz, D. EMBO J. (1989) [Pubmed]
  23. Two new Ypt GTPases are required for exit from the yeast trans-Golgi compartment. Jedd, G., Mulholland, J., Segev, N. J. Cell Biol. (1997) [Pubmed]
  24. Assembly of the ER to Golgi SNARE complex requires Uso1p. Sapperstein, S.K., Lupashin, V.V., Schmitt, H.D., Waters, M.G. J. Cell Biol. (1996) [Pubmed]
  25. A Rab requirement is not bypassed in SLY1-20 suppression. Ballew, N., Liu, Y., Barlowe, C. Mol. Biol. Cell (2005) [Pubmed]
  26. Sequence, expression and mutational analysis of BAF1, a transcriptional activator and ARS1-binding protein of the yeast Saccharomyces cerevisiae. Halfter, H., Kavety, B., Vandekerckhove, J., Kiefer, F., Gallwitz, D. EMBO J. (1989) [Pubmed]
  27. The yeast GTP-binding YPT1 protein and a mammalian counterpart are associated with the secretion machinery. Segev, N., Mulholland, J., Botstein, D. Cell (1988) [Pubmed]
  28. Biochemical properties of the ras-related YPT protein in yeast: a mutational analysis. Wagner, P., Molenaar, C.M., Rauh, A.J., Brökel, R., Schmitt, H.D., Gallwitz, D. EMBO J. (1987) [Pubmed]
  29. GTP hydrolysis is not important for Ypt1 GTPase function in vesicular transport. Richardson, C.J., Jones, S., Litt, R.J., Segev, N. Mol. Cell. Biol. (1998) [Pubmed]
  30. Overexpression of a dominant-negative allele of YPT1 inhibits growth and aspartyl protease secretion in Candida albicans. Lee, S.A., Mao, Y., Zhang, Z., Wong, B. Microbiology (Reading, Engl.) (2001) [Pubmed]
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