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Gene Review

VPS33  -  Vps33p

Saccharomyces cerevisiae S288c

Synonyms: CLS14, L8084.15, MET27, PEP14, Protein SLP1, ...
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High impact information on VPS33

  • VPS33B encodes a homolog of the class C yeast vacuolar protein sorting gene, Vps33, that contains a Sec1-like domain important in the regulation of vesicle-to-target SNARE complex formation and subsequent membrane fusion [1].
  • Cytosol made from a yeast strain deleted for the VPS33 gene was less efficient at driving transport [2].
  • A cell-free assay allows reconstitution of Vps33p-dependent transport to the yeast vacuole/lysosome [2].
  • Genetic interactions between VAM3 and a SEC1 family member, VPS33, suggest the two proteins may act together to direct the docking and/or fusion of multiple transport intermediates with the vacuole [3].
  • Mouse bf results from a mutation in Vps33a and thus is homologous to the yeast vacuolar protein-sorting mutant vps33 and Drosophila carnation (car) [4].

Biological context of VPS33

  • Disruptions or mutations of gene VPS33 are well known to impair the biogenesis and inheritance of the vacuolar compartment [5].
  • We also demonstrate that Vps33p acts at other steps, for vps33 mutants show severe defects in endocytosis at the late endosome [6].
  • Loss of function mutations in SEC1, SLY1, or SLP1 result in blocking of protein transport between distinct yeast sub-cellular compartments [7].
  • As comparative genome analysis can provide novel insights into gene evolution and function, we performed nucleotide and protein sequence comparisons of Vps33 homologues in different species to define their inter-relationships and evolution [8].
  • The SLP1 gene of Saccharomyces cerevisiae is essential for vacuolar morphogenesis and function [9].

Anatomical context of VPS33

  • These results indicate that the SLP1 (VPS33) gene is involved in the sorting of vacuolar proteins from the Golgi apparatus and their targeting to the vacuole and that it is required for the morphogenesis of vacuoles and subsequent expression of vacuolar functions [9].
  • However, during a chase, 20-40% of Vps33p fractionated with permeabilized cell membranes in a time-dependent fashion with a half-time of approximately 40 min [10].
  • The vesicle transport protein Vps33p is an ATP-binding protein that localizes to the cytosol in an energy-dependent manner [10].
  • Overall, these data support a model where Vps33p cycles between soluble and particulate forms in an ATP-dependent manner, which may facilitate the specificity of transport vesicle docking or targeting to the yeast lysosome/vacuole [10].

Associations of VPS33 with chemical compounds

  • Mutation or disruption of MET27 leads to a methionine requirement and affects S-adenosylmethionine (AdoMet)-mediated transcriptional control of genes involved in sulfur metabolism [5].
  • However, the methionine requirement of vps33 mutants has not been reported previously [5].
  • Interestingly, excess unlabeled ATP could enhance photoaffinity labeling of 8-azido-[alpha-32P]ATP to Vps33p, suggesting cooperative binding, which was not observed with excess GTP [10].
  • After depleting cellular ATP, Vps33p-GFP appeared to localize with a punctate morphology, which was also reversible upon restoring cells with glucose [10].
  • The N-ethylmaleimide-sensitive fusion protein homologue, Sec18p, a protein with known ATP binding and hydrolysis activity, displayed the same reversible energy-dependent sedimentation characteristics as Vps33p [10].

Physical interactions of VPS33

  • At the endosome, Vps33p and other class C members exist as a complex with Vps8p, a protein previously known to act in transport between the late Golgi and the endosome [6].

Regulatory relationships of VPS33

  • High copy PEP7/VAC1 suppresses vacuolar morphology defects of vps33 mutants [6].

Other interactions of VPS33

  • The Sec1/Munc18 protein, Vps33p, functions at the endosome and the vacuole of Saccharomyces cerevisiae [6].
  • Vacuolar morphology of vps33Delta cells resembles that of cells lacking both Vam3p and the endosomal syntaxin Pep12p, suggesting that Vps33p may function with these syntaxins at the vacuole and the endosome [6].
  • Vps33p also interacts with Pep12p, a known interactor of the SM protein Vps45p [6].
  • All effects caused by the overexpression of Ivy1p can be reset by simultaneously raising the amount of Vps33p [11].
  • A strain expressing Chimera-1 and lacking either vacuoles (vps33 mutant) or vacuolar polyphosphate (vtc1 mutant) was not viable when grown under conditions that favored AdoMet hyperaccumulation [12].

Analytical, diagnostic and therapeutic context of VPS33

  • In cell fractionation studies, Vps33p behaved as a cytosolic protein [13].
  • Carboxypeptidase Y in the delta slp1 mutant is localized mainly to the outsides of the cells. delta slp1 mutant cells have no prominent vacuolar structures but contain numerous vesicles in the cytoplasm, as seen by electron microscopy [9].


  1. Mutations in VPS33B, encoding a regulator of SNARE-dependent membrane fusion, cause arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome. Gissen, P., Johnson, C.A., Morgan, N.V., Stapelbroek, J.M., Forshew, T., Cooper, W.N., McKiernan, P.J., Klomp, L.W., Morris, A.A., Wraith, J.E., McClean, P., Lynch, S.A., Thompson, R.J., Lo, B., Quarrell, O.W., Di Rocco, M., Trembath, R.C., Mandel, H., Wali, S., Karet, F.E., Knisely, A.S., Houwen, R.H., Kelly, D.A., Maher, E.R. Nat. Genet. (2004) [Pubmed]
  2. A cell-free assay allows reconstitution of Vps33p-dependent transport to the yeast vacuole/lysosome. Vida, T., Gerhardt, B. J. Cell Biol. (1999) [Pubmed]
  3. A multispecificity syntaxin homologue, Vam3p, essential for autophagic and biosynthetic protein transport to the vacuole. Darsow, T., Rieder, S.E., Emr, S.D. J. Cell Biol. (1997) [Pubmed]
  4. The mouse organellar biogenesis mutant buff results from a mutation in Vps33a, a homologue of yeast vps33 and Drosophila carnation. Suzuki, T., Oiso, N., Gautam, R., Novak, E.K., Panthier, J.J., Suprabha, P.G., Vida, T., Swank, R.T., Spritz, R.A. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  5. The vacuolar compartment is required for sulfur amino acid homeostasis in Saccharomyces cerevisiae. Jacquemin-Faure, I., Thomas, D., Laporte, J., Cibert, C., Surdin-Kerjan, Y. Mol. Gen. Genet. (1994) [Pubmed]
  6. The Sec1/Munc18 protein, Vps33p, functions at the endosome and the vacuole of Saccharomyces cerevisiae. Subramanian, S., Woolford, C.A., Jones, E.W. Mol. Biol. Cell (2004) [Pubmed]
  7. The Sec1 family: a novel family of proteins involved in synaptic transmission and general secretion. Halachmi, N., Lev, Z. J. Neurochem. (1996) [Pubmed]
  8. Comparative evolutionary analysis of VPS33 homologues: genetic and functional insights. Gissen, P., Johnson, C.A., Gentle, D., Hurst, L.D., Doherty, A.J., O'Kane, C.J., Kelly, D.A., Maher, E.R. Hum. Mol. Genet. (2005) [Pubmed]
  9. The SLP1 gene of Saccharomyces cerevisiae is essential for vacuolar morphogenesis and function. Wada, Y., Kitamoto, K., Kanbe, T., Tanaka, K., Anraku, Y. Mol. Cell. Biol. (1990) [Pubmed]
  10. The vesicle transport protein Vps33p is an ATP-binding protein that localizes to the cytosol in an energy-dependent manner. Gerhardt, B., Kordas, T.J., Thompson, C.M., Patel, P., Vida, T. J. Biol. Chem. (1998) [Pubmed]
  11. A novel phospholipid-binding protein from the yeast Saccharomyces cerevisiae with dual binding specificities for the transport GTPase Ypt7p and the Sec1-related Vps33p. Lazar, T., Scheglmann, D., Gallwitz, D. Eur. J. Cell Biol. (2002) [Pubmed]
  12. Regulation of S-adenosylmethionine levels in Saccharomyces cerevisiae. Chan, S.Y., Appling, D.R. J. Biol. Chem. (2003) [Pubmed]
  13. Characterization of yeast Vps33p, a protein required for vacuolar protein sorting and vacuole biogenesis. Banta, L.M., Vida, T.A., Herman, P.K., Emr, S.D. Mol. Cell. Biol. (1990) [Pubmed]
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