Gene Symbol: VPS4
Description: AAA family ATPase VPS4
Alias: CSC1, DID6, END13, GRD13, VPL4, VPT10, AAA family ATPase VPS4
Species: Saccharomyces cerevisiae S288c
Products:     VPS4

Top Publications

  1. Dimaano C, Jones C, Hanono A, Curtiss M, Babst M. Ist1 regulates Vps4 localization and assembly. Mol Biol Cell. 2008;19:465-74 pubmed
    ..The dissociation of ESCRT machinery by the AAA-type ATPase Vps4 is a necessary late step in the formation of MVB vesicles...
  2. Nickerson D, West M, Henry R, Odorizzi G. Regulators of Vps4 ATPase activity at endosomes differentially influence the size and rate of formation of intralumenal vesicles. Mol Biol Cell. 2010;21:1023-32 pubmed publisher
    ..Disassembly of the ESCRT-III polymer and dissociation of its subunits from endosomes requires the Vps4 ATPase, the activity of which is controlled in vivo by regulatory proteins...
  3. Shestakova A, Curtiss M, Davies B, Katzmann D, Babst M. The linker region plays a regulatory role in assembly and activity of the Vps4 AAA ATPase. J Biol Chem. 2013;288:26810-9 pubmed publisher
    The AAA-type ATPase Vps4 functions with components of the ESCRT (endosomal sorting complex required for transport) machinery in membrane fission events that are essential for endosomal maturation, cytokinesis, and the formation of ..
  4. Lottridge J, Flannery A, Vincelli J, Stevens T. Vta1p and Vps46p regulate the membrane association and ATPase activity of Vps4p at the yeast multivesicular body. Proc Natl Acad Sci U S A. 2006;103:6202-7 pubmed
    ..These results reveal functional roles for the Vps46p and Vta1p proteins in regulating the ESCRT complex assembly/disassembly cycle in protein sorting at the yeast late endosome. ..
  5. Amerik A, Nowak J, Swaminathan S, Hochstrasser M. The Doa4 deubiquitinating enzyme is functionally linked to the vacuolar protein-sorting and endocytic pathways. Mol Biol Cell. 2000;11:3365-80 pubmed
    ..However, in cells lacking the Vps4/Did6 ATPase, a large fraction of Doa4-green fluorescent protein, like several other Vps factors, concentrates at the ..
  6. Xiao J, Xia H, Zhou J, Azmi I, Davies B, Katzmann D, et al. Structural basis of Vta1 function in the multivesicular body sorting pathway. Dev Cell. 2008;14:37-49 pubmed publisher
    ..Proper function of the MVB pathway requires reversible membrane association of the ESCRTs, a process catalyzed by Vps4 ATPase. Vta1 regulates the Vps4 activity, but its mechanism of action was poorly understood...
  7. Bowers K, Lottridge J, Helliwell S, Goldthwaite L, Luzio J, Stevens T. Protein-protein interactions of ESCRT complexes in the yeast Saccharomyces cerevisiae. Traffic. 2004;5:194-210 pubmed
    ..We propose the formation of a large multimeric complex on the endosome membrane consisting of ESCRTI, ESCRTII, ESCRTIII and other associated proteins. ..
  8. Azmi I, Davies B, Xiao J, Babst M, Xu Z, Katzmann D. ESCRT-III family members stimulate Vps4 ATPase activity directly or via Vta1. Dev Cell. 2008;14:50-61 pubmed publisher
    The AAA-ATPase Vps4 is critical for function of the MVB sorting pathway, which in turn impacts cellular phenomena ranging from receptor downregulation to viral budding to cytokinesis...
  9. Scott A, Chung H, Gonciarz Swiatek M, Hill G, Whitby F, Gaspar J, et al. Structural and mechanistic studies of VPS4 proteins. EMBO J. 2005;24:3658-69 pubmed
    b>VPS4 ATPases function in multivesicular body formation and in HIV-1 budding...

More Information


  1. Azmi I, Davies B, Dimaano C, Payne J, Eckert D, Babst M, et al. Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a conserved VSL region in Vta1. J Cell Biol. 2006;172:705-17 pubmed
    ..b>Vps4, an ATPase associated with a variety of cellular activities, is required late in the MVB sorting reaction to ..
  2. Yu Z, Gonciarz M, Sundquist W, Hill C, Jensen G. Cryo-EM structure of dodecameric Vps4p and its 2:1 complex with Vta1p. J Mol Biol. 2008;377:364-77 pubmed publisher
    The type I AAA (ATPase associated with a variety of cellular activities) ATPase Vps4 and its co-factor Vta1p/LIP5 function in membrane remodeling events that accompany cytokinesis, multivesicular body biogenesis, and retrovirus budding, ..
  3. Obita T, Saksena S, Ghazi Tabatabai S, Gill D, Perisic O, Emr S, et al. Structural basis for selective recognition of ESCRT-III by the AAA ATPase Vps4. Nature. 2007;449:735-9 pubmed publisher
    ..The AAA ATPase Vps4, which is central to endosomal traffic to lysosomes, retroviral budding and cytokinesis, dissociates ESCRT ..
  4. Rue S, Mattei S, Saksena S, Emr S. Novel Ist1-Did2 complex functions at a late step in multivesicular body sorting. Mol Biol Cell. 2008;19:475-84 pubmed
    ..Ist1-Did2 and Vta1-Vps60 form specific physical complexes, and, like Did2 and Vta1, Ist1 binds to the AAA-ATPase Vps4. We provide evidence that the ist1Delta mutation exhibits a synthetic interaction with mutations in VPS2 (DID4) ..
  5. Vajjhala P, Nguyen C, Landsberg M, Kistler C, Gan A, King G, et al. The Vps4 C-terminal helix is a critical determinant for assembly and ATPase activity and has elements conserved in other members of the meiotic clade of AAA ATPases. FEBS J. 2008;275:1427-49 pubmed publisher
    ..b>Vps4 is an AAA ATPase that functions in MVB sorting...
  6. Hartmann C, Chami M, Zachariae U, de Groot B, Engel A, Grutter M. Vacuolar protein sorting: two different functional states of the AAA-ATPase Vps4p. J Mol Biol. 2008;377:352-63 pubmed publisher
    The vacuolar protein sorting (Vps) pathway, in which Vps4 class I AAA-ATPases play a central role, regulates growth factor receptors, immune response, and developmental signaling, and participates in tumor suppression, apoptosis, and ..
  7. Babst M, Wendland B, Estepa E, Emr S. The Vps4p AAA ATPase regulates membrane association of a Vps protein complex required for normal endosome function. EMBO J. 1998;17:2982-93 pubmed
    ..of two previously uncharacterized class E Vps proteins, Vps24p and Vps32p/Snf7p, was also affected by mutations in VPS4. Upon inactivation of a temperature-conditional vps4 mutant, Vps24p and Vps32p/Snf7p rapidly accumulated in a large ..
  8. Babst M, Sato T, Banta L, Emr S. Endosomal transport function in yeast requires a novel AAA-type ATPase, Vps4p. EMBO J. 1997;16:1820-31 pubmed
    ..The vacuolar protein sorting (vps) mutant vps4 accumulates vacuolar, endocytic and late-Golgi markers in an aberrant multilamellar pre-vacuolar compartment...
  9. Monroe N, Han H, Gonciarz M, Eckert D, Karren M, Whitby F, et al. The oligomeric state of the active Vps4 AAA ATPase. J Mol Biol. 2014;426:510-25 pubmed publisher
    ..A component of this pathway, the AAA ATPase Vps4, provides energy for pathway progression...
  10. Nickerson D, West M, Odorizzi G. Did2 coordinates Vps4-mediated dissociation of ESCRT-III from endosomes. J Cell Biol. 2006;175:715-20 pubmed
    ..The subsequent dissociation of ESCRT complexes from endosomes requires Vps4, a member of the AAA family of adenosine triphosphatases...
  11. Shestakova A, Hanono A, Drosner S, Curtiss M, Davies B, Katzmann D, et al. Assembly of the AAA ATPase Vps4 on ESCRT-III. Mol Biol Cell. 2010;21:1059-71 pubmed publisher
    b>Vps4 is a key enzyme that functions in endosomal protein trafficking, cytokinesis, and retroviral budding. Vps4 activity is regulated by its recruitment from the cytoplasm to ESCRT-III, where the protein oligomerizes into an active ATPase...
  12. Gonciarz M, Whitby F, Eckert D, Kieffer C, Heroux A, Sundquist W, et al. Biochemical and structural studies of yeast Vps4 oligomerization. J Mol Biol. 2008;384:878-95 pubmed publisher
    ..As the only known enzyme in the ESCRT pathway, the AAA ATPase (ATPase associated with diverse cellular activities) Vps4 provides the energy required for multiple rounds of vesicle formation...
  13. Wollert T, Wunder C, Lippincott Schwartz J, Hurley J. Membrane scission by the ESCRT-III complex. Nature. 2009;458:172-7 pubmed publisher
    ..consists of Vps20, Snf7, Vps24 and Vps2 (also known as Did4), which assemble in that order and require the ATPase Vps4 for their disassembly...
  14. Russell M, Shideler T, Nickerson D, West M, Odorizzi G. Class E compartments form in response to ESCRT dysfunction in yeast due to hyperactivity of the Vps21 Rab GTPase. J Cell Sci. 2012;125:5208-20 pubmed publisher
    ..in response to transient ESCRT inactivation and recovery in yeast expressing the temperature-sensitive mutant vps4(ts) allele...
  15. Yeo S, Xu L, Ren J, Boulton V, Wagle M, Liu C, et al. Vps20p and Vta1p interact with Vps4p and function in multivesicular body sorting and endosomal transport in Saccharomyces cerevisiae. J Cell Sci. 2003;116:3957-70 pubmed
    ..We propose that Vps20p and Vta1p regulate Vps4p function in vivo. ..
  16. Wang P, Zhang Y, Li H, Chieu H, Munn A, Yang H. AAA ATPases regulate membrane association of yeast oxysterol binding proteins and sterol metabolism. EMBO J. 2005;24:2989-99 pubmed
    ..Deletion of VPS4 induced a dramatic increase in the membrane-associated pools of Osh6p and Osh7p and also caused a decrease in ..
  17. Xiao J, Xia H, Yoshino Koh K, Zhou J, Xu Z. Structural characterization of the ATPase reaction cycle of endosomal AAA protein Vps4. J Mol Biol. 2007;374:655-70 pubmed
    ..Disassembly of the ESCRTs is catalyzed by ATPase associated with various cellular activities (AAA) protein Vps4. Vps4 contains a single AAA domain and undergoes ATP-dependent quaternary structural change to disassemble the ..
  18. Yang B, Stjepanovic G, Shen Q, Martin A, Hurley J. Vps4 disassembles an ESCRT-III filament by global unfolding and processive translocation. Nat Struct Mol Biol. 2015;22:492-8 pubmed publisher
    The AAA+ ATPase Vps4 disassembles ESCRT-III and is essential for HIV-1 budding and other pathways. Vps4 is a paradigmatic member of a class of hexameric AAA+ ATPases that disassemble protein complexes without degradation...
  19. Shideler T, Nickerson D, Merz A, Odorizzi G. Ubiquitin binding by the CUE domain promotes endosomal localization of the Rab5 GEF Vps9. Mol Biol Cell. 2015;26:1345-56 pubmed publisher
    ..These results indicate that ubiquitin binding by the CUE domain promotes Vps9 function in endolysosomal membrane trafficking via promotion of localization. ..
  20. Nair U, Jotwani A, Geng J, Gammoh N, Richerson D, Yen W, et al. SNARE proteins are required for macroautophagy. Cell. 2011;146:290-302 pubmed publisher
    ..Thus, multiple SNARE-mediated fusion events are likely to be involved in autophagosome biogenesis. ..
  21. Jones C, Ott E, Keener J, Curtiss M, Sandrin V, Babst M. Regulation of membrane protein degradation by starvation-response pathways. Traffic. 2012;13:468-82 pubmed publisher
    ..Together, the data indicate that protein synthesis and turnover are linked by a common regulatory system that ensures adaptation and survival under nutrient-stress conditions. ..
  22. Inoue M, Kamikubo H, Kataoka M, Kato R, Yoshimori T, Wakatsuki S, et al. Nucleotide-dependent conformational changes and assembly of the AAA ATPase SKD1/VPS4B. Traffic. 2008;9:2180-9 pubmed publisher
    ..ATP hydrolysis would eliminate this interaction and subsequent nucleotide release causes the domains to rotate, which together lead to the disassembly of the SKD1 oligomer. ..
  23. Norgan A, Davies B, Azmi I, Schroeder A, Payne J, Lynch G, et al. Relief of autoinhibition enhances Vta1 activation of Vps4 via the Vps4 stimulatory element. J Biol Chem. 2013;288:26147-56 pubmed publisher
    ..The AAA-ATPase Vps4 is required for ESCRT function, and its full activity is dependent upon the co-factor Vta1...
  24. Webster B, Colombi P, Jäger J, Lusk C. Surveillance of nuclear pore complex assembly by ESCRT-III/Vps4. Cell. 2014;159:388-401 pubmed publisher
    ..Heh2 recruits the endosomal sorting complex required for transport (ESCRT)-III subunit Snf7 and the AAA-ATPase Vps4 to destabilize and clear defective NPC assembly intermediates...
  25. Weiss P, Huppert S, Kölling R. Analysis of the dual function of the ESCRT-III protein Snf7 in endocytic trafficking and in gene expression. Biochem J. 2009;424:89-97 pubmed publisher
    ..ESCRT-III subunits Vps20 and Vps24 were strongly increased by the mutations, whereas the interactions with proteins Vps4 and Bro1, acting downstream of ESCRT-III, were reduced...
  26. Adell M, Vogel G, Pakdel M, M ller M, Lindner H, Hess M, et al. Coordinated binding of Vps4 to ESCRT-III drives membrane neck constriction during MVB vesicle formation. J Cell Biol. 2014;205:33-49 pubmed publisher
    ..The AAA-adenosine triphosphatase Vps4 disassembles and recycles the ESCRT-III complex, thereby terminating the ESCRT pathway...
  27. Zhang F, Gaur N, Hasek J, Kim S, Qiu H, Swanson M, et al. Disrupting vesicular trafficking at the endosome attenuates transcriptional activation by Gcn4. Mol Cell Biol. 2008;28:6796-818 pubmed publisher
  28. Vajjhala P, Wong J, To H, Munn A. The beta domain is required for Vps4p oligomerization into a functionally active ATPase. FEBS J. 2006;273:2357-73 pubmed
    ..b>Vps4 is an AAA family ATPase which plays a key role in MVB sorting and facilitates transport through endosomes...
  29. Hayashi M, Fukuzawa T, Sorimachi H, Maeda T. Constitutive activation of the pH-responsive Rim101 pathway in yeast mutants defective in late steps of the MVB/ESCRT pathway. Mol Cell Biol. 2005;25:9478-90 pubmed
    ..Three identified suppressors-did4/vps2, vps24, and vps4-all belonged to "class E" vps mutants, which are commonly defective in multivesicular body sorting...
  30. Eguez L, Chung Y, Kuchibhatla A, Paidhungat M, Garrett S. Yeast Mn2+ transporter, Smf1p, is regulated by ubiquitin-dependent vacuolar protein sorting. Genetics. 2004;167:107-17 pubmed
    ..Because Smf1p is ubiquitinated in vivo, we propose that Smf1p is targeted to the vacuole for degradation by ubiquitination-dependent protein sorting. ..
  31. Harsay E, Schekman R. A subset of yeast vacuolar protein sorting mutants is blocked in one branch of the exocytic pathway. J Cell Biol. 2002;156:271-85 pubmed
    ..that vacuolar protein sorting mutants that block an endosome-mediated route to the vacuole, including vps1, pep12, vps4, and a temperature-sensitive clathrin mutant, missort cargo normally transported by dense exocytic vesicles, such ..
  32. Jensen L, Carroll M, Hall M, Harvey C, Beese S, Culotta V. Down-regulation of a manganese transporter in the face of metal toxicity. Mol Biol Cell. 2009;20:2810-9 pubmed publisher
    ..We provide evidence that manganese starvation is sensed within the lumen of the secretory pathway, whereas manganese toxicity is sensed within an extra-Golgi/cytosolic compartment of the cell. ..
  33. Yang D, Hurley J. Structural role of the Vps4-Vta1 interface in ESCRT-III recycling. Structure. 2010;18:976-84 pubmed publisher
    ..The final step in the ESCRT cycle is the disassembly of the ESCRT-III lattice by the AAA+ ATPase Vps4. Vps4 assembles on its membrane-bound ESCRT-III substrate with its cofactor, Vta1...
  34. Nebauer R, Rosenberger S, Daum G. Phosphatidylethanolamine, a limiting factor of autophagy in yeast strains bearing a defect in the carboxypeptidase Y pathway of vacuolar targeting. J Biol Chem. 2007;282:16736-43 pubmed
    ..We found that deletion of VPS4 and VPS36 caused impaired maturation of the vacuolar proaminopeptidase I (pAPI) via autophagy or the cytosol to ..
  35. Tomishige N, Noda Y, Adachi H, Shimoi H, Yoda K. SKG1, a suppressor gene of synthetic lethality of kex2Deltagas1Delta mutations, encodes a novel membrane protein that affects cell wall composition. Yeast. 2005;22:141-55 pubmed
    ..Thus SKG1 encodes a novel protein that affects the cell wall polymer composition in the growing region of the cell. ..
  36. Webster B, Thaller D, Jager J, Ochmann S, Borah S, Lusk C. Chm7 and Heh1 collaborate to link nuclear pore complex quality control with nuclear envelope sealing. EMBO J. 2016;35:2447-2467 pubmed
  37. Munn A, Riezman H. Endocytosis is required for the growth of vacuolar H(+)-ATPase-defective yeast: identification of six new END genes. J Cell Biol. 1994;127:373-86 pubmed
    ..and end11-1) show altered uptake of the endocytosed ligand, alpha-factor, and three (end12-1, end12-2, and end13-1) are probably defective in transfer of internalized material to the vacuole...
  38. Vild C, Xu Z. Vfa1 binds to the N-terminal microtubule-interacting and trafficking (MIT) domain of Vps4 and stimulates its ATPase activity. J Biol Chem. 2014;289:10378-86 pubmed publisher
    ..assembled molecular complexes on the membrane, and their disassembly requires the action of the AAA-ATPase Vps4. Vps4 is regulated by a multitude of ESCRT and ESCRT-related proteins...
  39. Tan J, Davies B, Payne J, Benson L, Katzmann D. Conformational Changes in the Endosomal Sorting Complex Required for the Transport III Subunit Ist1 Lead to Distinct Modes of ATPase Vps4 Regulation. J Biol Chem. 2015;290:30053-65 pubmed publisher
    ..The ATPase Vps4 remodels and disassembles ESCRT-III, but the manner in which Vps4 activity is coordinated with ESCRT-III function ..
  40. Curwin A, Brouwers N, Alonso Y Adell M, Teis D, Turacchio G, Parashuraman S, et al. ESCRT-III drives the final stages of CUPS maturation for unconventional protein secretion. elife. 2016;5: pubmed publisher
    ..secretion that reveals requirements for ESCRT-I, -II, and -III but, surprisingly, without the involvement of the Vps4 AAA-ATPase...
  41. Monroe N, Han H, Shen P, Sundquist W, Hill C. Structural basis of protein translocation by the Vps4-Vta1 AAA ATPase. elife. 2017;6: pubmed publisher
    ..reactions are driven by ESCRT pathways, which culminate in disassembly of ESCRT-III polymers by the AAA ATPase Vps4. We report a 4...
  42. Ren X, Hurley J. Structural basis for endosomal recruitment of ESCRT-I by ESCRT-0 in yeast. EMBO J. 2011;30:2130-9 pubmed publisher
    ..However, this site is non-essential for sorting of the ESCRT cargo Cps1. Taken together, these results show how a conserved motif/domain pair can evolve to use strikingly different binding modes in different organisms. ..
  43. Hoffman Sommer M, Kucharczyk R, Piekarska I, Kozlowska E, Rytka J. Mutations in the Saccharomyces cerevisiae vacuolar fusion proteins Ccz1, Mon1 and Ypt7 cause defects in cell cycle progression in a num1Delta background. Eur J Cell Biol. 2009;88:639-52 pubmed publisher
    ..Together, these results indicate that deregulation of the cell cycle in these mutants results from two separate mechanisms, one of which is related to calcium homeostasis. ..
  44. Vajjhala P, Catchpoole E, Nguyen C, Kistler C, Munn A. Vps4 regulates a subset of protein interactions at the multivesicular endosome. FEBS J. 2007;274:1894-907 pubmed
    ..Vacuolar protein sorting 4 (Vps4) is an AAA (ATPase associated with a variety of cellular activities) ATPase which has been proposed to play a ..
  45. Finken Eigen M, Röhricht R, Köhrer K. The VPS4 gene is involved in protein transport out of a yeast pre-vacuolar endosome-like compartment. Curr Genet. 1997;31:469-80 pubmed
    ..The mutant alleles causing the defects were identified as the members of the VPS4 gene locus, each harbouring single-point mutations leading to amino-acid exchanges at positions 233 (E233Q), 211 (..
  46. Nothwehr S, Bryant N, Stevens T. The newly identified yeast GRD genes are required for retention of late-Golgi membrane proteins. Mol Cell Biol. 1996;16:2700-7 pubmed
    ..All of the grd mutants exhibited significant mislocalization of A-ALP, as measured by determining the kinetics of A-ALP processing and by analyzing its ..
  47. Davies B, Norgan A, Payne J, Schulz M, Nichols M, TAN J, et al. Vps4 stimulatory element of the cofactor Vta1 contacts the ATPase Vps4 α7 and α9 to stimulate ATP hydrolysis. J Biol Chem. 2014;289:28707-18 pubmed publisher
    ..b>Vps4 ATPase activity modulates ESCRT function and is itself modulated by its cofactor Vta1 and its substrate ESCRT-III...
  48. Sciskala B, Kölling R. Interaction maps of the Saccharomyces cerevisiae ESCRT-III protein Snf7. Eukaryot Cell. 2013;12:1538-46 pubmed publisher
    ..b>Vps4 bound to individual Snf7 motifs but not to full-length Snf7...
  49. Arlt H, Perz A, Ungermann C. An overexpression screen in Saccharomyces cerevisiae identifies novel genes that affect endocytic protein trafficking. Traffic. 2011;12:1592-603 pubmed publisher
    ..Among the novel proteins, we identify Yer128w as an endosomal protein that interacts with the AAA-ATPase Vps4, and therefore named it Vfa1 (Vps Four-Associated 1)...
  50. Han H, Monroe N, Votteler J, Shakya B, Sundquist W, Hill C. Binding of Substrates to the Central Pore of the Vps4 ATPase Is Autoinhibited by the Microtubule Interacting and Trafficking (MIT) Domain and Activated by MIT Interacting Motifs (MIMs). J Biol Chem. 2015;290:13490-9 pubmed publisher
    ..The AAA ATPase Vps4 is recruited to membrane necks shortly before fission, where it catalyzes disassembly of the ESCRT-III lattice...