Vacuolar protein sorting-associated protein

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Function

Vacuolar protein sorting-associated protein (Vps) are part of Endosomal Sorting Complex Required for Transport (ESCRT) that performs the topologically unique membrane bending and scission reaction away from the cytoplasm. This process is required for the multivesicular body pathway, cytokinesis and HIV budding. There are five distinct ESCRT complexes (0,I,II,III,Vps4) with distinct functions[1].

  • Vps4, Vps4A, Vps4B complex catalyzes the disassembly of the ESCRT-III filament in an ATP-driven reaction. Vps4 proteins are required for centrosome and spindle maintenance[2].
  • Vps9A activates Rab5 to GTP-bound form[3].
  • Vps15 may function as a G protein β subunit at the endosome [4].
  • Vps23 is involved in appropriate sorting of receptors within the yast endocytic pathway and is part of the ESCRT-I complex[5]
  • Vps25 is part of the ESCRT-II complex which contains two copies of the protein. It induces a conformational switch that converts inactive Vps20 into an active nucleator for Snf7 oligomerization[6].
  • Vps26A and Vps26B are part of the Vps29-Vps35-Vps26 retromer which mediates transport of transmembrane proteins from endosomes to the trans-Golgi network[7].
  • Vps27 is part of the ESCRT-0 complex
  • Vps36 is part of the ESCRT-II complex


Disease

Relevance

Vps25 in Drosophila possesses several properties of tumor repressor[8].

Structural highlights

Caption for this structure

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3D structures of vacuolar protein sorting-associated protein3D structures of vacuolar protein sorting-associated protein

Updated on 11-December-2018

ReferencesReferences

  1. Schmidt O, Teis D. The ESCRT machinery. Curr Biol. 2012 Feb 21;22(4):R116-20. doi: 10.1016/j.cub.2012.01.028. PMID:22361144 doi:http://dx.doi.org/10.1016/j.cub.2012.01.028
  2. Morita E, Colf LA, Karren MA, Sandrin V, Rodesch CK, Sundquist WI. Human ESCRT-III and VPS4 proteins are required for centrosome and spindle maintenance. Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):12889-94. doi:, 10.1073/pnas.1005938107. Epub 2010 Jun 29. PMID:20616062 doi:http://dx.doi.org/10.1073/pnas.1005938107
  3. Goh T, Uchida W, Arakawa S, Ito E, Dainobu T, Ebine K, Takeuchi M, Sato K, Ueda T, Nakano A. VPS9a, the common activator for two distinct types of Rab5 GTPases, is essential for the development of Arabidopsis thaliana. Plant Cell. 2007 Nov;19(11):3504-15. Epub 2007 Nov 30. PMID:18055610 doi:10.1105/tpc.107.053876
  4. Heenan EJ, Vanhooke JL, Temple BR, Betts L, Sondek JE, Dohlman HG. Structure and function of Vps15 in the endosomal G protein signaling pathway. Biochemistry. 2009 Jul 14;48(27):6390-401. PMID:19445518 doi:10.1021/bi900621w
  5. Bishop N, Woodman P. TSG101/mammalian VPS23 and mammalian VPS28 interact directly and are recruited to VPS4-induced endosomes. J Biol Chem. 2001 Apr 13;276(15):11735-42. Epub 2000 Dec 27. PMID:11134028 doi:http://dx.doi.org/10.1074/jbc.M009863200
  6. Teis D, Saksena S, Judson BL, Emr SD. ESCRT-II coordinates the assembly of ESCRT-III filaments for cargo sorting and multivesicular body vesicle formation. EMBO J. 2010 Mar 3;29(5):871-83. doi: 10.1038/emboj.2009.408. Epub 2010 Feb 4. PMID:20134403 doi:http://dx.doi.org/10.1038/emboj.2009.408
  7. Bugarcic A, Zhe Y, Kerr MC, Griffin J, Collins BM, Teasdale RD. Vps26A and Vps26B subunits define distinct retromer complexes. Traffic. 2011 Dec;12(12):1759-73. doi: 10.1111/j.1600-0854.2011.01284.x. Epub, 2011 Oct 17. PMID:21920005 doi:http://dx.doi.org/10.1111/j.1600-0854.2011.01284.x
  8. Thompson BJ, Mathieu J, Sung HH, Loeser E, Rorth P, Cohen SM. Tumor suppressor properties of the ESCRT-II complex component Vps25 in Drosophila. Dev Cell. 2005 Nov;9(5):711-20. doi: 10.1016/j.devcel.2005.09.020. PMID:16256745 doi:http://dx.doi.org/10.1016/j.devcel.2005.09.020

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Michal Harel, Alexander Berchansky