Proteopedia

Vacuolar protein sorting-associated protein


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 (MVP) pathway, cytokinesis and HIV budding. There are five distinct ESCRT complexes (0,I,II,III,Vps4) with distinct functions[1]. The retromer comprises 2 functional subcomplexes: the cargo-selective one which contains Vps35, Vps29 and Vps26 and the sorting nexin subcomplex which tubulate the endosomal membrane[2]. The Vps proteins are found in yeast. The human homologs are called also chromatin-modifying protein or Charged multivesicular body protein (CHMP)[3].

  • 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[4].
  • Vps9A activates Rab5 to GTP-bound form[5].
  • Vps15 may function as a G protein β subunit at the endosome [6].
  • Vps23 is involved in appropriate sorting of receptors within the yast endocytic pathway and is part of the ESCRT-I complex[7]
  • 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[8].
  • Vps26A and Vps26B are part of the Vps29-Vps35-Vps26 retromer which mediates transport of transmembrane proteins from endosomes to the trans-Golgi network[9].
  • Vps27 interacts with the lipid phosphatidylinositol-3-phosphate and this interaction activates the MVP sorting pathway. Vps27 is part of the ESCRT-I complex[10].
  • Vps28 C-terminal links ESCRT-I and ESCRT-II[11].
  • Vps29, Vps30 and Vps35 are required for the recycling of Vps10p from the prevacuolar endosome back to the Golgi[12].
  • Vps33 binds SNARE domains[13].
  • Vps33A is part of the homotypic fusion and vacuole sorting comples which is required for fusion of intracellular compartments with lysosomes[14].
  • Vps34 is a class III Phosphoinositide 3-Kinases[15].
  • Vps36 contains a ubiquitin-binding domain and is required for vacuolar sorting of ubiqinated membrane proteins. Vps36 is part of the ESCRT-II complex[16].
  • Vps46 is part of the ESCRT-II complex[17].
  • Vps53 C-terminal is important for binding endosome-derived vesicles[18].
  • Vps54 is part of the Golgi-associated retrograde protein complex (GARP) of vesicle sorting proteins[19].
  • Vps60 is involved in filament maturation[20].
  • Vps74 is a sensor of phosphatidylinositol 4-kinase level on medial Golgi cisternae[21].
  • Vps75 is a histone chaperone which functions in chromatin assembly and disassembly[22].
  • Vps Vta1 is a cofactor ov Vps4[23].

Disease

Mutations in Vps53 cause progressive cerebello-cerebral atrophy type 2[24]. Mutations in Vps54 in mice cause motor neuron disease[25]. Dysfunction of the retromer is implicated in neurodegenerative disease like Alzheimer disease, Parkinson's disease and Frontotemporal lobar degeneration[26].

Relevance

Vps25 in Drosophila possesses several properties of tumor repressor[27]. Vps36 is downregulated in advanced prostate cancer[28].

  • Vps26A

Structural highlights

Vps75 interacts with histone acetyltransferase through three interfacing areas. . The other two interfaces are on each side of the catalytic enclosure and contain hydrophobic contacts and salt bridges[29].

  • .
  • .

3D structures of vacuolar protein sorting-associated protein

Vacuolar protein sorting-associated protein 3D structures

Vps75 (deepskyblue and green) complex with histone acetyltransferase (magenta) and sulfate (PDB code 3q68)

Drag the structure with the mouse to rotate

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. ↑ Seaman MN, Harbour ME, Tattersall D, Read E, Bright N. Membrane recruitment of the cargo-selective retromer subcomplex is catalysed by the small GTPase Rab7 and inhibited by the Rab-GAP TBC1D5. J Cell Sci. 2009 Jul 15;122(Pt 14):2371-82. Epub 2009 Jun 16. PMID:19531583 doi:http://dx.doi.org/jcs.048686
  3. ↑ Tsang HT, Connell JW, Brown SE, Thompson A, Reid E, Sanderson CM. A systematic analysis of human CHMP protein interactions: additional MIT domain-containing proteins bind to multiple components of the human ESCRT III complex. Genomics. 2006 Sep;88(3):333-46. PMID:16730941 doi:10.1016/j.ygeno.2006.04.003
  4. ↑ 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
  5. ↑ 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
  6. ↑ 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
  7. ↑ 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
  8. ↑ 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
  9. ↑ 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
  10. ↑ Katzmann DJ, Stefan CJ, Babst M, Emr SD. Vps27 recruits ESCRT machinery to endosomes during MVB sorting. J Cell Biol. 2003 Aug 4;162(3):413-23. PMID:12900393 doi:http://dx.doi.org/10.1083/jcb.200302136
  11. ↑ Gill DJ, Teo H, Sun J, Perisic O, Veprintsev DB, Emr SD, Williams RL. Structural insight into the ESCRT-I/-II link and its role in MVB trafficking. EMBO J. 2007 Jan 24;26(2):600-12. Epub 2007 Jan 11. PMID:17215868
  12. ↑ Seaman MN, Marcusson EG, Cereghino JL, Emr SD. Endosome to Golgi retrieval of the vacuolar protein sorting receptor, Vps10p, requires the function of the VPS29, VPS30, and VPS35 gene products. J Cell Biol. 1997 Apr 7;137(1):79-92. PMID:9105038
  13. ↑ Lobingier BT, Merz AJ. Sec1/Munc18 protein Vps33 binds to SNARE domains and the quaternary SNARE complex. Mol Biol Cell. 2012 Dec;23(23):4611-22. doi: 10.1091/mbc.E12-05-0343. Epub 2012, Oct 10. PMID:23051737 doi:http://dx.doi.org/10.1091/mbc.E12-05-0343
  14. ↑ Wartosch L, Gunesdogan U, Graham SC, Luzio JP. Recruitment of VPS33A to HOPS by VPS16 Is Required for Lysosome Fusion with Endosomes and Autophagosomes. Traffic. 2015 Jul;16(7):727-42. doi: 10.1111/tra.12283. Epub 2015 Apr 30. PMID:25783203 doi:http://dx.doi.org/10.1111/tra.12283
  15. ↑ Su WC, Chao TC, Huang YL, Weng SC, Jeng KS, Lai MM. Rab5 and class III phosphoinositide 3-kinase Vps34 are involved in hepatitis C virus NS4B-induced autophagy. J Virol. 2011 Oct;85(20):10561-71. doi: 10.1128/JVI.00173-11. Epub 2011 Aug 10. PMID:21835792 doi:http://dx.doi.org/10.1128/JVI.00173-11
  16. ↑ Slagsvold T, Aasland R, Hirano S, Bache KG, Raiborg C, Trambaiolo D, Wakatsuki S, Stenmark H. Eap45 in mammalian ESCRT-II binds ubiquitin via a phosphoinositide-interacting GLUE domain. J Biol Chem. 2005 May 20;280(20):19600-6. Epub 2005 Mar 7. PMID:15755741 doi:http://dx.doi.org/10.1074/jbc.M501510200
  17. ↑ Yue Q, Yu Q, Yang Q, Xu Y, Guo Y, Blissard GW, Li Z. Distinct Roles of Cellular ESCRT-I and ESCRT-III Proteins in Efficient Entry and Egress of Budded Virions of Autographa californica Multiple Nucleopolyhedrovirus. J Virol. 2017 Dec 14;92(1). pii: JVI.01636-17. doi: 10.1128/JVI.01636-17. Print, 2018 Jan 1. PMID:29046462 doi:http://dx.doi.org/10.1128/JVI.01636-17
  18. ↑ Vasan N, Hutagalung A, Novick P, Reinisch KM. Structure of a C-terminal fragment of its Vps53 subunit suggests similarity of Golgi-associated retrograde protein (GARP) complex to a family of tethering complexes. Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14176-81. Epub 2010 Jul 26. PMID:20660722 doi:10.1073/pnas.1009419107
  19. ↑ Meisler MH, Russ C, Montgomery KT, Greenway M, Ennis S, Hardiman O, Figlewicz DA, Quenneville NR, Conibear E, Brown RH Jr. Evaluation of the Golgi trafficking protein VPS54 (wobbler) as a candidate for ALS. Amyotroph Lateral Scler. 2008 Jun;9(3):141-8. doi: 10.1080/17482960801934403. PMID:18574757 doi:http://dx.doi.org/10.1080/17482960801934403
  20. ↑ Kohler JR. Mos10 (Vps60) is required for normal filament maturation in Saccharomyces cerevisiae. Mol Microbiol. 2003 Sep;49(5):1267-85. PMID:12940986
  21. ↑ Lievense H, Kalantar-Zadeh K, Lukowsky LR, Molnar MZ, Duong U, Nissenson A, Krishnan M, Krediet R, Mehrotra R. Relationship of body size and initial dialysis modality on subsequent transplantation, mortality and weight gain of ESRD patients. Nephrol Dial Transplant. 2012 Sep;27(9):3631-8. doi: 10.1093/ndt/gfs131. Epub, 2012 May 2. PMID:22553372 doi:http://dx.doi.org/10.1093/ndt/gfs131
  22. ↑ Xue YM, Kowalska AK, Grabowska K, Przybyt K, Cichewicz MA, Del Rosario BC, Pemberton LF. Histone chaperones Nap1 and Vps75 regulate histone acetylation during transcription elongation. Mol Cell Biol. 2013 Apr;33(8):1645-56. doi: 10.1128/MCB.01121-12. Epub 2013 Feb, 11. PMID:23401858 doi:http://dx.doi.org/10.1128/MCB.01121-12
  23. ↑ Yang D, Hurley JH. Structural role of the Vps4-Vta1 interface in ESCRT-III recycling. Structure. 2010 Aug 11;18(8):976-84. PMID:20696398 doi:10.1016/j.str.2010.04.014
  24. ↑ Feinstein M, Flusser H, Lerman-Sagie T, Ben-Zeev B, Lev D, Agamy O, Cohen I, Kadir R, Sivan S, Leshinsky-Silver E, Markus B, Birk OS. VPS53 mutations cause progressive cerebello-cerebral atrophy type 2 (PCCA2). J Med Genet. 2014 May;51(5):303-8. doi: 10.1136/jmedgenet-2013-101823. Epub 2014 , Feb 27. PMID:24577744 doi:http://dx.doi.org/10.1136/jmedgenet-2013-101823
  25. ↑ Schmitt-John T, Drepper C, Mussmann A, Hahn P, Kuhlmann M, Thiel C, Hafner M, Lengeling A, Heimann P, Jones JM, Meisler MH, Jockusch H. Mutation of Vps54 causes motor neuron disease and defective spermiogenesis in the wobbler mouse. Nat Genet. 2005 Nov;37(11):1213-5. Epub 2005 Oct 23. PMID:16244655 doi:10.1038/ng1661
  26. ↑ Reitz C. Retromer Dysfunction and Neurodegenerative Disease. Curr Genomics. 2018 May;19(4):279-288. doi: 10.2174/1389202919666171024122809. PMID:29755290 doi:http://dx.doi.org/10.2174/1389202919666171024122809
  27. ↑ 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
  28. ↑ Worst TS, Meyer Y, Gottschalt M, Weis CA, von Hardenberg J, Frank C, Steidler A, Michel MS, Erben P. RAB27A, RAB27B and VPS36 are downregulated in advanced prostate cancer and show functional relevance in prostate cancer cells. Int J Oncol. 2017 Mar;50(3):920-932. doi: 10.3892/ijo.2017.3872. Epub 2017 Feb, 10. PMID:28197629 doi:http://dx.doi.org/10.3892/ijo.2017.3872
  29. ↑ Su D, Hu Q, Zhou H, Thompson JR, Xu RM, Zhang Z, Mer G. Structure and histone binding properties of the Vps75-Rtt109 chaperone-lysine acetyltransferase complex. J Biol Chem. 2011 Mar 22. PMID:21454705 doi:10.1074/jbc.C111.220715

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