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Gene Review

YPT6  -  Rab family GTPase YPT6

Saccharomyces cerevisiae S288c

Synonyms: GTP-binding protein YPT6, L8479.11, YLR262C
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High impact information on YPT6

  • The gene, GYP6 (GAP of Ypt6 protein), encodes a protein of 458 amino acids which is highly specific for the Ypt6 protein and shows little or no cross-reactivity with other Ypt/Rab family members or with H-Ras p21 [1].
  • We previously identified Sys1p as a high copy number suppressor of Ypt6 GTPase-deficient yeast mutants that are defective in endosome-to-Golgi transport [2].
  • A screen for mutants that, like ypt6, specifically impair the growth of imh1 cells led to the identification of RIC1 [3].
  • Interestingly, the deletions of GYP1 and YPT6 were synthetic lethal, raising the possibility that at least two distinct pathways are involved in recycling of membrane material [4].
  • Based on previous studies with ypt6 deletion mutants, a regulatory role of the GTPase either in protein retrieval to the trans-Golgi network or in forward transport between the endoplasmic reticulum (ER) and early Golgi compartments was proposed [5].

Biological context of YPT6

  • Deletion of YPT6 in yeast produces a phenotype showing temperature-sensitive growth and partial missorting of the vacuolar enzyme, carboxypeptidase Y [6].
  • Structural and functional analysis of a novel coiled-coil protein involved in Ypt6 GTPase-regulated protein transport in yeast [7].
  • However, deletion of SYS1 and/or SYS2 in the ypt6 null mutant enhances defects in vacuolar protein sorting and in cell growth [6].
  • The predicted amino acid sequence was highly homologous to the mammalian and yeast counterparts, H.Rab6 and Ryh1/Ypt6, respectively [8].
  • Furthermore, we show that the yeast GTPase-activating protein Gyp6, shown to be specifically required to control the GTP hydrolysis of the yeast Ypt6 protein, could interact with tobacco GTP-binding proteins [9].

Anatomical context of YPT6

  • In Saccharomyces cerevisiae, the YPT6 gene encodes the homologue of the mammalian Rab6 protein found in the Golgi apparatus [6].
  • Mutation of the Rab6 homologue of Saccharomyces cerevisiae, YPT6, inhibits both early Golgi function and ribosome biosynthesis [10].
  • In budding yeast Ypt6 is required for recycling of membrane proteins from endosomes back to the Golgi [11].
  • A biochemical approach based on the affinity purification of Ypt6:GTP-interacting proteins from yeast cytosol led to the identification of two conserved Ypt6 effectors, the tetrameric VFT complex and Sgm1 [11].

Associations of YPT6 with chemical compounds

  • Cloning of extragenic suppressors of the ts allele of YPT6 has revealed two additional proteins that influence the secretory pathway: Ssd1p, a suppressor of many mutations, and Imh1p, which bears some homology to the C-terminal portion of the cytoskeletal proteins integrin and myosin [10].

Regulatory relationships of YPT6

  • Here we show that overexpression of YPT1 suppresses the growth and secretion defects of a ypt6 temperature-sensitive (ts) strain [12].

Other interactions of YPT6

  • Genetic interaction between YPT6 and YPT1 in Saccharomyces cerevisiae [12].
  • SYS1, originally discovered as a multicopy suppressor of defects caused by the absence of the Rab GTPase YPT6, was identified as a multicopy suppressor of ric1Delta [13].
  • Whereas protein secretion was not significantly affected in these mutants, the processing of alpha-factor precursor by the Kex2 protease was inhibited, suggesting a function of YPT6 and its null mutant suppressors in transport between the late Golgi and a prevacuolar, endosome-like compartment [6].


  1. A yeast GTPase-activating protein that interacts specifically with a member of the Ypt/Rab family. Strom, M., Vollmer, P., Tan, T.J., Gallwitz, D. Nature (1993) [Pubmed]
  2. An acidic sequence of a putative yeast Golgi membrane protein binds COPII and facilitates ER export. Votsmeier, C., Gallwitz, D. EMBO J. (2001) [Pubmed]
  3. Ric1p and Rgp1p form a complex that catalyses nucleotide exchange on Ypt6p. Siniossoglou, S., Peak-Chew, S.Y., Pelham, H.R. EMBO J. (2000) [Pubmed]
  4. The GTPase-activating enzyme Gyp1p is required for recycling of internalized membrane material by inactivation of the Rab/Ypt GTPase Ypt1p. Lafourcade, C., Galan, J.M., Gloor, Y., Haguenauer-Tsapis, R., Peter, M. Mol. Cell. Biol. (2004) [Pubmed]
  5. Biochemical and genetic evidence for the involvement of yeast Ypt6-GTPase in protein retrieval to different Golgi compartments. Luo, Z., Gallwitz, D. J. Biol. Chem. (2003) [Pubmed]
  6. Isolation and characterization of SYS genes from yeast, multicopy suppressors of the functional loss of the transport GTPase Ypt6p. Tsukada, M., Gallwitz, D. J. Cell. Sci. (1996) [Pubmed]
  7. Structural and functional analysis of a novel coiled-coil protein involved in Ypt6 GTPase-regulated protein transport in yeast. Tsukada, M., Will, E., Gallwitz, D. Mol. Biol. Cell (1999) [Pubmed]
  8. A small GTP-binding protein from Arabidopsis thaliana functionally complements the yeast YPT6 null mutant. Bednarek, S.Y., Reynolds, T.L., Schroeder, M., Grabowski, R., Hengst, L., Gallwitz, D., Raikhel, N.V. Plant Physiol. (1994) [Pubmed]
  9. Characterization of membrane-bound small GTP-binding proteins from Nicotiana tabacum. Haizel, T., Merkle, T., Turck, F., Nagy, F. Plant Physiol. (1995) [Pubmed]
  10. Mutation of the Rab6 homologue of Saccharomyces cerevisiae, YPT6, inhibits both early Golgi function and ribosome biosynthesis. Li, B., Warner, J.R. J. Biol. Chem. (1996) [Pubmed]
  11. Affinity purification of Ypt6 effectors and identification of TMF/ARA160 as a Rab6 interactor. Siniossoglou, S. Meth. Enzymol. (2005) [Pubmed]
  12. Genetic interaction between YPT6 and YPT1 in Saccharomyces cerevisiae. Li, B., Warner, J.R. Yeast (1998) [Pubmed]
  13. Ric1p and the Ypt6p GTPase function in a common pathway required for localization of trans-Golgi network membrane proteins. Bensen, E.S., Yeung, B.G., Payne, G.S. Mol. Biol. Cell (2001) [Pubmed]
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