VAPB explained

Vesicle-associated membrane protein-associated protein B/C is a protein that in humans is encoded by the VAPB gene.^{[1] [2]} The VAPB gene is found on the 20th human chromosome. Together with VAPA, it forms the VAP protein family.

Function

The protein encoded by this gene is a type IV membrane protein found in plasma and intracellular vesicle membranes. The encoded protein is found as a homodimer and as a heterodimer with VAPA. This protein also can interact with VAMP1 and VAMP2 and may be involved in vesicle trafficking.^[2]

Like VAPA, VAPB binds to proteins that contain a FFAT motif.^[3] Considerable interest in VAPB has arisen because mutations in this protein are associated with rare, familial forms of motor neuron disease (also called amyotrophic lateral sclerosis and Lou Gehrig's disease).^[4]

References

Further reading

• Bastepe M, Pincus JE, Jüppner H . Two frequent tetra-nucleotide repeat polymorphisms between VAPB and STX16 on chromosome 20q13 . Molecular and Cellular Probes . 13 . 6 . 449–51 . Dec 1999 . 10657150 . 10.1006/mcpr.1999.0271 .
• Paumet F, Le Mao J, Martin S, Galli T, David B, Blank U, Roa M . Soluble NSF attachment protein receptors (SNAREs) in RBL-2H3 mast cells: functional role of syntaxin 4 in exocytosis and identification of a vesicle-associated membrane protein 8-containing secretory compartment . Journal of Immunology . 164 . 11 . 5850–7 . Jun 2000 . 10820264 . 10.4049/jimmunol.164.11.5850 . free .
• 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 . Proceedings of the National Academy of Sciences of the United States of America . 97 . 17 . 9543–8 . Aug 2000 . 10931946 . 16901 . 10.1073/pnas.160270997 . 2000PNAS...97.9543H . free .
• Polgár J, Chung SH, Reed GL . Vesicle-associated membrane protein 3 (VAMP-3) and VAMP-8 are present in human platelets and are required for granule secretion . Blood . 100 . 3 . 1081–3 . Aug 2002 . 12130530 . 10.1182/blood.V100.3.1081 . 36597939 .
• Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J . Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides . Nature Biotechnology . 21 . 5 . 566–9 . May 2003 . 12665801 . 10.1038/nbt810 . 23783563 .
• Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A . The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment . Genome Research . 13 . 10 . 2265–70 . Oct 2003 . 12975309 . 403697 . 10.1101/gr.1293003 .
• Nishimura AL, Mitne-Neto M, Silva HC, Oliveira JR, Vainzof M, Zatz M . A novel locus for late onset amyotrophic lateral sclerosis/motor neurone disease variant at 20q13 . Journal of Medical Genetics . 41 . 4 . 315–20 . Apr 2004 . 15060112 . 1735732 . 10.1136/jmg.2003.013029 .
• Nishimura AL, Mitne-Neto M, Silva HC, Richieri-Costa A, Middleton S, Cascio D, Kok F, Oliveira JR, Gillingwater T, Webb J, Skehel P, Zatz M . A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis . American Journal of Human Genetics . 75 . 5 . 822–31 . Nov 2004 . 15372378 . 1182111 . 10.1086/425287 .
• Amarilio R, Ramachandran S, Sabanay H, Lev S . Differential regulation of endoplasmic reticulum structure through VAP-Nir protein interaction . The Journal of Biological Chemistry . 280 . 7 . 5934–44 . Feb 2005 . 15545272 . 10.1074/jbc.M409566200 . free .
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . Oct 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
• Hamamoto I, Nishimura Y, Okamoto T, Aizaki H, Liu M, Mori Y, Abe T, Suzuki T, Lai MM, Miyamura T, Moriishi K, Matsuura Y . Human VAP-B is involved in hepatitis C virus replication through interaction with NS5A and NS5B . Journal of Virology . 79 . 21 . 13473–82 . Nov 2005 . 16227268 . 1262604 . 10.1128/JVI.79.21.13473-13482.2005 .
• Nousiainen M, Silljé HH, Sauer G, Nigg EA, Körner R . Phosphoproteome analysis of the human mitotic spindle . Proceedings of the National Academy of Sciences of the United States of America . 103 . 14 . 5391–6 . Apr 2006 . 16565220 . 1459365 . 10.1073/pnas.0507066103 . 2006PNAS..103.5391N . free .
• Perry RJ, Ridgway ND . Oxysterol-binding protein and vesicle-associated membrane protein-associated protein are required for sterol-dependent activation of the ceramide transport protein . Molecular Biology of the Cell . 17 . 6 . 2604–16 . Jun 2006 . 16571669 . 1474796 . 10.1091/mbc.E06-01-0060 .
• Conforti FL, Sprovieri T, Mazzei R, Ungaro C, Tessitore A, Tedeschi G, Patitucci A, Magariello A, Gabriele A, Labella V, Simone IL, Majorana G, Monsurrò MR, Valentino P, Muglia M, Quattrone A . Sporadic ALS is not associated with VAPB gene mutations in Southern Italy . Journal of Negative Results in Biomedicine . 5 . 7 . 2006 . 16729899 . 1481594 . 10.1186/1477-5751-5-7 . free .
• Kanekura K, Nishimoto I, Aiso S, Matsuoka M . Characterization of amyotrophic lateral sclerosis-linked P56S mutation of vesicle-associated membrane protein-associated protein B (VAPB/ALS8) . The Journal of Biological Chemistry . 281 . 40 . 30223–33 . Oct 2006 . 16891305 . 10.1074/jbc.M605049200 . free .

Notes and References

1. Nishimura Y, Hayashi M, Inada H, Tanaka T . Molecular cloning and characterization of mammalian homologues of vesicle-associated membrane protein-associated (VAMP-associated) proteins . Biochemical and Biophysical Research Communications . 254 . 1 . 21–6 . Jan 1999 . 9920726 . 10.1006/bbrc.1998.9876 .
2. Web site: Entrez Gene: VAPB VAMP (vesicle-associated membrane protein)-associated protein B and C.
3. Loewen CJ, Roy A, Levine TP . A conserved ER targeting motif in three families of lipid binding proteins and in Opi1p binds VAP . The EMBO Journal . 22 . 9 . 2025–35 . May 2003 . 12727870 . 10.1093/emboj/cdg201 . 156073.
4. Nishimura AL, Mitne-Neto M, Silva HC, Richieri-Costa A, Middleton S, Cascio D, Kok F, Oliveira JR, Gillingwater T, Webb J, Skehel P, Zatz M . A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis . American Journal of Human Genetics . 75 . 5 . 822–31 . Nov 2004 . 15372378 . 10.1086/425287 . 1182111.