VPS4A explained

Vacuolar protein sorting-associated protein 4A is a protein that in humans is encoded by the VPS4A gene.^{[1] [2] [3]}

Function

The protein encoded by this gene is a member of the AAA protein family (ATPases associated with diverse cellular activities), and is the homolog of the yeast Vps4 protein. In humans, two paralogs of the yeast protein have been identified. They share a high degree of amino acid sequence similarity with each other, and also with yeast Vps4 and mouse proteins. Functional studies indicate that both human paralogs associate with the endosomal compartments, and are involved in intracellular protein trafficking, similar to Vps4 protein in yeast. The gene encoding this paralog has been mapped to chromosome 16; the gene for the other resides on chromosome 18.^[3]

Interactions

VPS4A has been shown to interact with CHMP1A.^[4]

Further reading

• Scheuring S, Bodor O, Röhricht RA, Müller S, Beyer A, Köhrer K . Cloning, characterisation, and functional expression of the Mus musculus SKD1 gene in yeast demonstrates that the mouse SKD1 and the yeast VPS4 genes are orthologues and involved in intracellular protein trafficking . Gene . 234 . 1 . 149–59 . 1999 . 10393249 . 10.1016/S0378-1119(99)00163-8 .
• Hu RM, Han ZG, Song HD, Peng YD, Huang QH, Ren SX, Gu YJ, Huang CH, Li YB, Jiang CL, Fu G, Zhang QH, Gu BW, Dai M, Mao YF, Gao GF, Rong R, Ye M, Zhou J, Xu SH, Gu J, Shi JX, Jin WR, Zhang CK, Wu TM, Huang GY, Chen Z, Chen MD, Chen JL . Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning . Proc. Natl. Acad. Sci. U.S.A. . 97 . 17 . 9543–8 . 2000 . 10931946 . 16901 . 10.1073/pnas.160270997 . 2000PNAS...97.9543H . free .
• Howard TL, Stauffer DR, Degnin CR, Hollenberg SM . CHMP1 functions as a member of a newly defined family of vesicle trafficking proteins . J. Cell Sci. . 114 . Pt 13 . 2395–404 . 2002 . 10.1242/jcs.114.13.2395 . 11559748 .
• Tanaka H, Fujita H, Katoh H, Mori K, Negishi M . Vps4-A (vacuolar protein sorting 4-A) is a binding partner for a novel Rho family GTPase, Rnd2 . Biochem. J. . 365 . Pt 2 . 349–53 . 2002 . 11931639 . 1222680 . 10.1042/BJ20020062 .
• Nara A, Mizushima N, Yamamoto A, Kabeya Y, Ohsumi Y, Yoshimori T . SKD1 AAA ATPase-dependent endosomal transport is involved in autolysosome formation . Cell Struct. Funct. . 27 . 1 . 29–37 . 2002 . 11937716 . 10.1247/csf.27.29 . free .
• Chagnon P, Michaud J, Mitchell G, Mercier J, Marion JF, Drouin E, Rasquin-Weber A, Hudson TJ, Richter A . A Missense Mutation (R565W) in Cirhin (FLJ14728) in North American Indian Childhood Cirrhosis . Am. J. Hum. Genet. . 71 . 6 . 1443–9 . 2003 . 12417987 . 378590 . 10.1086/344580 .
• Beyer A, Scheuring S, Müller S, Mincheva A, Lichter P, Köhrer K . Comparative sequence and expression analyses of four mammalian VPS4 genes . Gene . 305 . 1 . 47–59 . 2003 . 12594041 . 10.1016/S0378-1119(02)01205-2 .
• Katoh K, Shibata H, Suzuki H, Nara A, Ishidoh K, Kominami E, Yoshimori T, Maki M . The ALG-2-interacting protein Alix associates with CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting . J. Biol. Chem. . 278 . 40 . 39104–13 . 2003 . 12860994 . 10.1074/jbc.M301604200 . free .
• Strack B, Calistri A, Craig S, Popova E, Göttlinger HG . AIP1/ALIX is a binding partner for HIV-1 p6 and EIAV p9 functioning in virus budding . Cell . 114 . 6 . 689–99 . 2003 . 14505569 . 10.1016/S0092-8674(03)00653-6 . 10733770 . free .
• von Schwedler UK, Stuchell M, Müller B, Ward DM, Chung HY, Morita E, Wang HE, Davis T, He GP, Cimbora DM, Scott A, Kräusslich HG, Kaplan J, Morham SG, Sundquist WI . The protein network of HIV budding . Cell . 114 . 6 . 701–13 . 2003 . 14505570 . 10.1016/S0092-8674(03)00714-1 . 16894972 . free .
• Sachse M, Strous GJ, Klumperman J . ATPase-deficient hVPS4 impairs formation of internal endosomal vesicles and stabilizes bilayered clathrin coats on endosomal vacuoles . J. Cell Sci. . 117 . Pt 9 . 1699–708 . 2004 . 15075231 . 10.1242/jcs.00998 . free .
• Lin Y, Kimpler LA, Naismith TV, Lauer JM, Hanson PI . Interaction of the mammalian endosomal sorting complex required for transport (ESCRT) III protein hSnf7-1 with itself, membranes, and the AAA+ ATPase SKD1 . J. Biol. Chem. . 280 . 13 . 12799–809 . 2005 . 15632132 . 10.1074/jbc.M413968200 . free .
• Scott A, Gaspar J, Stuchell-Brereton MD, Alam SL, Skalicky JJ, Sundquist WI . Structure and ESCRT-III protein interactions of the MIT domain of human VPS4A . Proc. Natl. Acad. Sci. U.S.A. . 102 . 39 . 13813–8 . 2005 . 16174732 . 1236530 . 10.1073/pnas.0502165102 . 2005PNAS..10213813S . free .
• 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 . 88 . 3 . 333–46 . 2006 . 16730941 . 10.1016/j.ygeno.2006.04.003 . free .
• Chen VY, Posada MM, Blazer LL, Zhao T, Rosania GR . The role of the VPS4A-exosome pathway in the intrinsic egress route of a DNA-binding anticancer drug . Pharm. Res. . 23 . 8 . 1687–95 . 2007 . 16841193 . 10.1007/s11095-006-9043-0 . 2777033 .
• Lambert C, Döring T, Prange R . Hepatitis B Virus Maturation Is Sensitive to Functional Inhibition of ESCRT-III, Vps4, and γ2-Adaptin . J. Virol. . 81 . 17 . 9050–60 . 2007 . 17553870 . 1951427 . 10.1128/JVI.00479-07 .

Notes and References

1. Bishop N, Woodman P . ATPase-defective Mammalian VPS4 Localizes to Aberrant Endosomes and Impairs Cholesterol Trafficking . Mol Biol Cell . 11 . 1 . 227–39 . April 2000 . 10637304 . 14770 . 10.1091/mbc.11.1.227 .
2. Scheuring S, Röhricht RA, Schöning-Burkhardt B, Beyer A, Müller S, Abts HF, Köhrer K . Mammalian cells express two VPS4 proteins both of which are involved in intracellular protein trafficking . J Mol Biol . 312 . 3 . 469–80 . September 2001 . 11563910 . 10.1006/jmbi.2001.4917 .
3. Web site: Entrez Gene: VPS4A vacuolar protein sorting 4 homolog A (S. cerevisiae).
4. Howard TL, Stauffer DR, Degnin CR, Hollenberg SM . CHMP1 functions as a member of a newly defined family of vesicle trafficking proteins . J. Cell Sci. . 114 . Pt 13 . 2395–404 . July 2001 . 10.1242/jcs.114.13.2395 . 11559748 .