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Gene Review: 

VPS4B  -  vacuolar protein sorting 4 homolog B (S....

Homo sapiens

Synonyms: Cell migration-inducing gene 1 protein, MIG1, Protein SKD1, SKD1, SKD1B, ...
 
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Disease relevance of VPS4B

  • Candidate gene analysis of BCL2, however, excludes most of this gene, except its promoter region, and draws attention to the neighboring gene VPS4B, part of the endosomal protein-sorting machinery ESCRT-III which is involved in several neurodegenerative diseases [1].
  • Finally, HIV-1 budding was inhibited by mutations in a loop that projects into the center of the modeled hVPS4B rings, suggesting that hVPS4B may release the assembled ESCRT machinery by pulling ESCRT-III substrates up into the central pore [2].
 

High impact information on VPS4B

  • SKD1/VPS4B is an AAA+ (ATPase associated with a variety of cellular activities) protein involved in multivesicular body (MVB) biogenesis [3].
  • SKD1(E235Q) associated with NPC1 on the endosomal membrane, whereas wild-type SKD1 associated with NPC1 only when cells were depleted of cholesterol [4].
  • Similar to the action of a mutant SKD1 protein, overexpression of a fusion derivative of human CHMP1 dilates endosomal compartments and disrupts the normal distribution of several endosomal markers [5].
  • Expression of mutant human VPS4-A (E228Q) and VPS4-B (E235Q) proteins, harbouring single amino acid exchanges in their AAA domains, induced dominant-negative vacuolar protein sorting defects in wild-type yeast cells in both cases [6].
  • The vacuolar protein sorting defect of vps4 mutant yeast cells was complemented completely by heterologous expressed human VPS4-B protein, and partially by the human VPS4-A protein [6].
 

Biological context of VPS4B

 

Other interactions of VPS4B

References

  1. Fine-mapping and candidate gene analysis of bovine spinal muscular atrophy. Krebs, S., Medugorac, I., Russ, I., Ossent, P., Bleul, U., Schmahl, W., Förster, M. Mamm. Genome (2006)
  2. Structural and mechanistic studies of VPS4 proteins. Scott, A., Chung, H.Y., Gonciarz-Swiatek, M., Hill, G.C., Whitby, F.G., Gaspar, J., Holton, J.M., Viswanathan, R., Ghaffarian, S., Hill, C.P., Sundquist, W.I. EMBO J. (2005)
  3. Interaction of the mammalian endosomal sorting complex required for transport (ESCRT) III protein hSnf7-1 with itself, membranes, and the AAA+ ATPase SKD1. Lin, Y., Kimpler, L.A., Naismith, T.V., Lauer, J.M., Hanson, P.I. J. Biol. Chem. (2005)
  4. Cholesterol depletion facilitates ubiquitylation of NPC1 and its association with SKD1/Vps4. Ohsaki, Y., Sugimoto, Y., Suzuki, M., Hosokawa, H., Yoshimori, T., Davies, J.P., Ioannou, Y.A., Vanier, M.T., Ohno, K., Ninomiya, H. J. Cell. Sci. (2006)
  5. CHMP1 functions as a member of a newly defined family of vesicle trafficking proteins. Howard, T.L., Stauffer, D.R., Degnin, C.R., Hollenberg, S.M. J. Cell. Sci. (2001)
  6. Mammalian cells express two VPS4 proteins both of which are involved in intracellular protein trafficking. Scheuring, S., Röhricht, R.A., Schöning-Burkhardt, B., Beyer, A., Müller, S., Abts, H.F., Köhrer, K. J. Mol. Biol. (2001)
  7. Identification of a novel mammalian member of the NSF/CDC48p/Pas1p/TBP-1 family through heterologous expression in yeast. Périer, F., Coulter, K.L., Liang, H., Radeke, C.M., Gaber, R.F., Vandenberg, C.A. FEBS Lett. (1994)
  8. Comparative sequence and expression analyses of four mammalian VPS4 genes. Beyer, A., Scheuring, S., Müller, S., Mincheva, A., Lichter, P., Köhrer, K. Gene (2003)
 

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