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Gene Review

VPS21  -  Rab family GTPase VPS21

Saccharomyces cerevisiae S288c

Synonyms: GTP-binding protein YPT51, VPS12, VPT12, Vacuolar protein sorting-associated protein 21, Vacuolar protein-targeting protein 12, ...
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High impact information on VPS21

  • Membrane fusion also required the rab protein Vps21p [1].
  • Using a PCR approach to identify rab5 homologs in Saccharomyces cerevisiae, two genes encoding proteins with 54 and 52% identity to rab5, YPT51 and YPT53 have been identified [2].
  • Endocytic delivery to the vacuole of two markers, lucifer yellow CH (LY) and alpha-factor, was inhibited in delta ypt51 mutants and aggravated in the double ypt51ypt52 and triple ypt51ypt52ypt53 mutants, suggesting a requirement for these small GTPases in endocytic membrane traffic [2].
  • VPS21 encodes a 22 kDa protein that binds GTP and fractionates with subcellular membranes [3].
  • VPS21 encodes a rab5-like GTP binding protein that is required for the sorting of yeast vacuolar proteins [3].

Biological context of VPS21

  • We have constructed an activated allele of VPS21, a yeast Rab protein involved in vacuolar protein sorting, and demonstrated an allele-specific interaction between Vps21p and Vac1p [4].
  • The class D VPS genes include VPS21, PEP12, and VPS45, which appear to encode components of a membrane fusion complex involved in Golgi-to-endosome transport [5].
  • Vps21p is a member of the Rab family of small Ras-like GTPases and shows strong homology to the mammalian Rab5 protein, which is involved in endocytosis and the homotypic fusion of early endosomes [5].
  • Point mutations constructed within these conserved regions inactivate Vps21p function; the mutant cells missort and secrete the soluble vacuolar hydrolase carboxypeptidase Y (CPY) [3].
  • Mutant analysis indicates that the association with a membrane(s) is dependent on geranylgeranylation of the C-terminal cysteine residue(s) of Vps21p [3].

Anatomical context of VPS21


Associations of VPS21 with chemical compounds

  • The yeast Rab5 ortholog Vps21p is activated by its guanine nucleotide exchange factor Vps9p [8].
  • We present the 1.5 A high-resolution crystal structure of Ypt51 in its active, GppNHp-bound conformation [9].
  • The transport blockade can be achieved by deleting a GTPase of the endocytic pathway, Ypt51p, or ethanol [10].
  • Chloroquine affects the compartments of the late endocytic pathway, and no effect is seen on transfection in a strain that is defective for YPT51 and accumulates the DNA in the early endocytic intermediates [10].

Physical interactions of VPS21


Co-localisations of VPS21

  • Cdc50p colocalized with Vps21p in endosomal compartments and was also localized to the class E compartment in the vps27 mutant [12].

Regulatory relationships of VPS21


Other interactions of VPS21

  • Using an in vitro assay which reconstitutes Gdi1p-mediated membrane loading of Rab, this mutant Gdi1p was found to be defective in loading of Vps21p but not Ypt1p [6].
  • This association was found to depend on the function of Vps21p, a member of the Rab/Ypt/Sec4 family of small GTPases [7].
  • One of them, Gyp1p, acts on Sec4p, Ypt1p, Ypt7p, and Ypt51p in vitro [13].
  • These results implicate Vac1p as an effector of Vps21p and as a novel Sec1p-family-binding protein [14].
  • By contrast, a vps21 mutant produces a synthetic defect with lte1 in proprotein processing, as well as a synthetic growth defect [15].

Analytical, diagnostic and therapeutic context of VPS21


  1. The Tlg SNARE complex is required for TGN homotypic fusion. Brickner, J.H., Blanchette, J.M., Sipos, G., Fuller, R.S. J. Cell Biol. (2001) [Pubmed]
  2. Role of three rab5-like GTPases, Ypt51p, Ypt52p, and Ypt53p, in the endocytic and vacuolar protein sorting pathways of yeast. Singer-Krüger, B., Stenmark, H., Düsterhöft, A., Philippsen, P., Yoo, J.S., Gallwitz, D., Zerial, M. J. Cell Biol. (1994) [Pubmed]
  3. VPS21 encodes a rab5-like GTP binding protein that is required for the sorting of yeast vacuolar proteins. Horazdovsky, B.F., Busch, G.R., Emr, S.D. EMBO J. (1994) [Pubmed]
  4. The phosphatidylinositol 3-phosphate binding protein Vac1p interacts with a Rab GTPase and a Sec1p homologue to facilitate vesicle-mediated vacuolar protein sorting. Tall, G.G., Hama, H., DeWald, D.B., Horazdovsky, B.F. Mol. Biol. Cell (1999) [Pubmed]
  5. VPS21 controls entry of endocytosed and biosynthetic proteins into the yeast prevacuolar compartment. Gerrard, S.R., Bryant, N.J., Stevens, T.H. Mol. Biol. Cell (2000) [Pubmed]
  6. GDP dissociation inhibitor domain II required for Rab GTPase recycling. Gilbert, P.M., Burd, C.G. J. Biol. Chem. (2001) [Pubmed]
  7. A novel RING finger protein, Vps8p, functionally interacts with the small GTPase, Vps21p, to facilitate soluble vacuolar protein localization. Horazdovsky, B.F., Cowles, C.R., Mustol, P., Holmes, M., Emr, S.D. J. Biol. Chem. (1996) [Pubmed]
  8. Vps9p CUE domain ubiquitin binding is required for efficient endocytic protein traffic. Davies, B.A., Topp, J.D., Sfeir, A.J., Katzmann, D.J., Carney, D.S., Tall, G.G., Friedberg, A.S., Deng, L., Chen, Z., Horazdovsky, B.F. J. Biol. Chem. (2003) [Pubmed]
  9. High-resolution crystal structure of S. cerevisiae Ypt51(DeltaC15)-GppNHp, a small GTP-binding protein involved in regulation of endocytosis. Esters, H., Alexandrov, K., Constantinescu, A.T., Goody, R.S., Scheidig, A.J. J. Mol. Biol. (2000) [Pubmed]
  10. Endocytosis is involved in DNA uptake in yeast. Neukamm, B., Stahl, U., Lang, C. Biochim. Biophys. Acta (2002) [Pubmed]
  11. Vps9p is a guanine nucleotide exchange factor involved in vesicle-mediated vacuolar protein transport. Hama, H., Tall, G.G., Horazdovsky, B.F. J. Biol. Chem. (1999) [Pubmed]
  12. Cdc50p, a conserved endosomal membrane protein, controls polarized growth in Saccharomyces cerevisiae. Misu, K., Fujimura-Kamada, K., Ueda, T., Nakano, A., Katoh, H., Tanaka, K. Mol. Biol. Cell (2003) [Pubmed]
  13. Yeast rab GTPase-activating protein Gyp1p localizes to the Golgi apparatus and is a negative regulator of Ypt1p. Du, L.L., Novick, P. Mol. Biol. Cell (2001) [Pubmed]
  14. Vac1p coordinates Rab and phosphatidylinositol 3-kinase signaling in Vps45p-dependent vesicle docking/fusion at the endosome. Peterson, M.R., Burd, C.G., Emr, S.D. Curr. Biol. (1999) [Pubmed]
  15. A role for Lte1p (a low temperature essential protein involved in mitosis) in proprotein processing in the yeast secretory pathway. Zhao, X., Chang, A.Y., Toh-E, A., Arvan, P. J. Biol. Chem. (2007) [Pubmed]
  16. Visualization of receptor-mediated endocytosis in yeast. Mulholland, J., Konopka, J., Singer-Kruger, B., Zerial, M., Botstein, D. Mol. Biol. Cell (1999) [Pubmed]
  17. Yeast Ypt51p and mammalian Rab5: counterparts with similar function in the early endocytic pathway. Singer-Krüger, B., Stenmark, H., Zerial, M. J. Cell. Sci. (1995) [Pubmed]
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