VPS4A

Vacuolar protein sorting-associated protein 4A is a protein that in humans is encoded by the VPS4A gene.[5][6][7]

VPS4A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1YXR, 2JQ9, 2K3W
Identifiers
Aliases	VPS4A, SKD1, SKD1A, SKD2, VPS4, VPS4-1, vacuolar protein sorting 4 homolog A
External IDs	OMIM: 609982 MGI: 1890520 HomoloGene: 69132 GeneCards: VPS4A
Gene location (Human) Chr. Chromosome 16 (human)[1] Band 16q22.1 Start 69,311,350 bp[1] End 69,326,939 bp[1]
Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8|8 D3 Start 107,031,222 bp[2] End 107,045,755 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • nucleotide binding • protein domain specific binding • microtubule-severing ATPase activity • protein C-terminus binding • GO:0001948 protein binding • hydrolase activity • ATP binding • ATPase activity • GO:0032403 macromolecular complex binding Cellular component • cytoplasm • ESCRT III complex • cytosol • endosome • late endosome • centrosome • spindle pole • vacuolar membrane • late endosome membrane • Flemming body • membrane • cell membrane • midbody • early endosome • perinuclear region of cytoplasm • lysosome • extracellular exosome • cell nucleus • endosome membrane Biological process • late endosomal microautophagy • endosomal vesicle fusion • viral shedding • abscission • viral budding via host ESCRT complex • nucleus organization • GO:0019067 viral life cycle • multivesicular body assembly • vacuole organization • vesicle uncoating • regulation of protein localization • cell division • intracellular cholesterol transport • ESCRT complex disassembly • vesicle budding from membrane • ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway • transport • protein transport • positive regulation of viral release from host cell • positive regulation of viral life cycle • ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway • cell cycle • negative regulation of cytokinesis • cell separation after cytokinesis • mitotic metaphase plate congression • positive regulation of exosomal secretion • vesicle-mediated transport • regulation of protein localization to plasma membrane • ESCRT III complex disassembly • cytoplasmic microtubule organization • endosomal transport • macroautophagy • positive regulation of viral budding via host ESCRT complex • actomyosin contractile ring contraction • protein targeting to lysosome • nuclear envelope organization • nuclear envelope reassembly • mitotic cytokinesis checkpoint • cytoskeleton-dependent cytokinesis • midbody abscission Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	27183	116733
Ensembl	ENSG00000132612	ENSMUSG00000031913
UniProt	Q9UN37	Q8VEJ9
RefSeq (mRNA)	NM_013245	NM_126165
RefSeq (protein)	NP_037377 NP_037377.1	NP_569053
Location (UCSC)	Chr 16: 69.31 – 69.33 Mb	Chr 8: 107.03 – 107.05 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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. The former share a high degree of aa sequence similarity with each other, and also with yeast Vps4 and mouse Skd1 proteins. The mouse Skd1 (suppressor of K+ transport defect 1) has been shown to be really a yeast Vps4 ortholog. 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.[7]

Interactions

VPS4A has been shown to interact with CHMP1A.[8]

References

1. GRCh38: Ensembl release 89: ENSG00000132612 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000031913 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Bishop N, Woodman P (April 2000). "ATPase-defective Mammalian VPS4 Localizes to Aberrant Endosomes and Impairs Cholesterol Trafficking". Mol Biol Cell. 11 (1): 227–39. doi:10.1091/mbc.11.1.227. PMC 14770. PMID 10637304.
6. Scheuring S, Röhricht RA, Schöning-Burkhardt B, Beyer A, Müller S, Abts HF, Köhrer K (September 2001). "Mammalian cells express two VPS4 proteins both of which are involved in intracellular protein trafficking". J Mol Biol. 312 (3): 469–80. doi:10.1006/jmbi.2001.4917. PMID 11563910.
7. "Entrez Gene: VPS4A vacuolar protein sorting 4 homolog A (S. cerevisiae)".
8. Howard TL, Stauffer DR, Degnin CR, Hollenberg SM (July 2001). "CHMP1 functions as a member of a newly defined family of vesicle trafficking proteins". J. Cell Sci. 114 (Pt 13): 2395–404. PMID 11559748.

Further reading

• Scheuring S, Bodor O, Röhricht RA, Müller S, Beyer A, Köhrer K (1999). "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. doi:10.1016/S0378-1119(99)00163-8. PMID 10393249.
• 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 (2000). "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. doi:10.1073/pnas.160270997. PMC 16901. PMID 10931946.
• Howard TL, Stauffer DR, Degnin CR, Hollenberg SM (2002). "CHMP1 functions as a member of a newly defined family of vesicle trafficking proteins". J. Cell Sci. 114 (Pt 13): 2395–404. PMID 11559748.
• Tanaka H, Fujita H, Katoh H, Mori K, Negishi M (2002). "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. doi:10.1042/BJ20020062. PMC 1222680. PMID 11931639.
• Nara A, Mizushima N, Yamamoto A, Kabeya Y, Ohsumi Y, Yoshimori T (2002). "SKD1 AAA ATPase-dependent endosomal transport is involved in autolysosome formation". Cell Struct. Funct. 27 (1): 29–37. doi:10.1247/csf.27.29. PMID 11937716.
• Chagnon P, Michaud J, Mitchell G, Mercier J, Marion JF, Drouin E, Rasquin-Weber A, Hudson TJ, Richter A (2003). "A Missense Mutation (R565W) in Cirhin (FLJ14728) in North American Indian Childhood Cirrhosis". Am. J. Hum. Genet. 71 (6): 1443–9. doi:10.1086/344580. PMC 378590. PMID 12417987.
• Beyer A, Scheuring S, Müller S, Mincheva A, Lichter P, Köhrer K (2003). "Comparative sequence and expression analyses of four mammalian VPS4 genes". Gene. 305 (1): 47–59. doi:10.1016/S0378-1119(02)01205-2. PMID 12594041.
• Katoh K, Shibata H, Suzuki H, Nara A, Ishidoh K, Kominami E, Yoshimori T, Maki M (2003). "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. doi:10.1074/jbc.M301604200. PMID 12860994.
• Strack B, Calistri A, Craig S, Popova E, Göttlinger HG (2003). "AIP1/ALIX is a binding partner for HIV-1 p6 and EIAV p9 functioning in virus budding". Cell. 114 (6): 689–99. doi:10.1016/S0092-8674(03)00653-6. PMID 14505569.
• 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 (2003). "The protein network of HIV budding". Cell. 114 (6): 701–13. doi:10.1016/S0092-8674(03)00714-1. PMID 14505570.
• Sachse M, Strous GJ, Klumperman J (2004). "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. doi:10.1242/jcs.00998. PMID 15075231.
• Lin Y, Kimpler LA, Naismith TV, Lauer JM, Hanson PI (2005). "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. doi:10.1074/jbc.M413968200. PMID 15632132.
• Scott A, Gaspar J, Stuchell-Brereton MD, Alam SL, Skalicky JJ, Sundquist WI (2005). "Structure and ESCRT-III protein interactions of the MIT domain of human VPS4A". Proc. Natl. Acad. Sci. U.S.A. 102 (39): 13813–8. doi:10.1073/pnas.0502165102. PMC 1236530. PMID 16174732.
• Tsang HT, Connell JW, Brown SE, Thompson A, Reid E, Sanderson CM (2006). "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. doi:10.1016/j.ygeno.2006.04.003. PMID 16730941.
• Chen VY, Posada MM, Blazer LL, Zhao T, Rosania GR (2007). "The role of the VPS4A-exosome pathway in the intrinsic egress route of a DNA-binding anticancer drug". Pharm. Res. 23 (8): 1687–95. doi:10.1007/s11095-006-9043-0. PMID 16841193.
• Lambert C, Döring T, Prange R (2007). "Hepatitis B Virus Maturation Is Sensitive to Functional Inhibition of ESCRT-III, Vps4, and γ2-Adaptin". J. Virol. 81 (17): 9050–60. doi:10.1128/JVI.00479-07. PMC 1951427. PMID 17553870.