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Gene Review

VPS41  -  Vps41p

Saccharomyces cerevisiae S288c

Synonyms: CVT8, D446, FET2, SVL2, VAM2, ...
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High impact information on VPS41

  • Intriguingly, Yck3 mediates phosphorylation of the HOPS subunit Vps41, a bi-functional protein involved in both budding and fusion during vacuole biogenesis [1].
  • This screen identified PAN1, a gene required for normal endocytosis, and VPS41, a gene required for vacuolar fusion and protein targeting, suggesting a role for Mot3 in the regulation of membrane-related genes [2].
  • Like other VAM-encoded proteins, which are needed for homotypic vacuole fusion, we now report that Vam2p and its associated protein Vam6p/Vps39p are needed on each vacuole partner for homotypic fusion [3].
  • A previous study has shown that a large protein complex containing Vps39 and Vps41 functions as a downstream effector of the active, GTP-bound form of Ypt7, a rab GTPase required for the fusion of vesicular intermediates with the vacuole (Price, A., D. Seals, W. Wickner, and C. Ungermann. 2000. J. Cell Biol. 148:1231-1238) [4].
  • Vam2p/Vps41p is known to be required for transport vesicles with vacuolar cargo to bud from the Golgi [3].

Biological context of VPS41


Anatomical context of VPS41

  • Deletion of the VAM2 and VAM6 functions resulted in accumulation of numerous vacuole-related structures of 200-400 nm in diameter that were much smaller than the normal vacuoles [8].
  • Large portions of Vam2p and Vam6p were fractionated into a vacuolar enriched fraction, indicating that they were localized mainly in the vacuolar membranes [8].
  • These data indicate that a homo-oligomeric form of Vps41p is required for the formation of ALP containing vesicles at the Golgi complex via interactions with AP-3 [5].

Associations of VPS41 with chemical compounds

  • The epitope-tagged Vam2p and Vam6p remained in the sedimentable fractions in the presence of Triton X-100, but they were extracted by urea or NaCl [8].

Other interactions of VPS41

  • Loss of functions of Vam2p and Vam6p resulted in inefficient processings of a set of vacuolar proteins, including proteinase A, proteinase B, and carboxypeptidase Y (CPY), and in severely defective maturation of another vacuolar protein, alkaline phosphatase [8].
  • Upon priming by Sec18p/NSF and ATP, Vam2/6p is released as a 38S subcomplex that binds Ypt7p to initiate docking [9].
  • Sequencing analysis of these VPS41 alleles revealed mutations encoding amino acid changes in two distinct domains of Vps41p: a conserved N-terminal domain and a C-terminal clathrin heavy-chain repeat (CHCR) domain [5].


  1. The vacuolar kinase Yck3 maintains organelle fragmentation by regulating the HOPS tethering complex. LaGrassa, T.J., Ungermann, C. J. Cell Biol. (2005) [Pubmed]
  2. Mot3 is a transcriptional repressor of ergosterol biosynthetic genes and is required for normal vacuolar function in Saccharomyces cerevisiae. Hongay, C., Jia, N., Bard, M., Winston, F. EMBO J. (2002) [Pubmed]
  3. Proteins needed for vesicle budding from the Golgi complex are also required for the docking step of homotypic vacuole fusion. Price, A., Wickner, W., Ungermann, C. J. Cell Biol. (2000) [Pubmed]
  4. New component of the vacuolar class C-Vps complex couples nucleotide exchange on the Ypt7 GTPase to SNARE-dependent docking and fusion. Wurmser, A.E., Sato, T.K., Emr, S.D. J. Cell Biol. (2000) [Pubmed]
  5. Vps41p function in the alkaline phosphatase pathway requires homo-oligomerization and interaction with AP-3 through two distinct domains. Darsow, T., Katzmann, D.J., Cowles, C.R., Emr, S.D. Mol. Biol. Cell (2001) [Pubmed]
  6. Role of a VPS41 homologue in starvation response, intracellular survival and virulence of Cryptococcus neoformans. Liu, X., Hu, G., Panepinto, J., Williamson, P.R. Mol. Microbiol. (2006) [Pubmed]
  7. The docking stage of yeast vacuole fusion requires the transfer of proteins from a cis-SNARE complex to a Rab/Ypt protein. Price, A., Seals, D., Wickner, W., Ungermann, C. J. Cell Biol. (2000) [Pubmed]
  8. Vam2/Vps41p and Vam6/Vps39p are components of a protein complex on the vacuolar membranes and involved in the vacuolar assembly in the yeast Saccharomyces cerevisiae. Nakamura, N., Hirata, A., Ohsumi, Y., Wada, Y. J. Biol. Chem. (1997) [Pubmed]
  9. A Ypt/Rab effector complex containing the Sec1 homolog Vps33p is required for homotypic vacuole fusion. Seals, D.F., Eitzen, G., Margolis, N., Wickner, W.T., Price, A. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
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