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Gene Review

Mvp  -  major vault protein

Mus musculus

Synonyms: 2310009M24Rik, LRP, MVP, Major vault protein, VAULT1
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Disease relevance of Mvp


Psychiatry related information on Mvp


High impact information on Mvp

  • The low density lipoprotein receptor-related protein (LRP) is a large multifunctional clearance receptor that has been implicated in the hepatic uptake of chylomicron remnants and in the removal of protease-inhibitor complexes from the circulation and from the extracellular space [6].
  • Whereas LRP activity was normal, livers from treated mice incorporated significantly less sulfate into heparan sulfate proteoglycans (HSPG) than did controls [7].
  • Our results clearly demonstrate that two independent receptor systems, LRP and the mannose receptor, are involved in the hepatic clearance of t-PA [8].
  • Two distinct clearance mechanisms, which are mediated by the low density lipoprotein receptor-related protein (LRP) on liver parenchymal cells and by the mannose receptor on liver endothelial cells, have been described [8].
  • Using deletion constructs, the critical region in LRP that modulates APP processing was mapped to a seven peptide domain around the second NPXY domain (residues 4504-4510) [5].

Chemical compound and disease context of Mvp


Biological context of Mvp


Anatomical context of Mvp

  • Neither the MVP(-/-) embryonic stem cells nor the MVP(-/-) bone marrow cells showed an increased sensitivity to any of the drugs examined, as compared with wild-type cells [1].
  • There was no significant activation of either the MVP or VPARP promoters in drug-resistant cell lines in comparison to their parental, drug-sensitive counterparts [12].
  • We now demonstrate that binding of lactoferrin, Pseudomonas exotoxin A, and lipoprotein lipase to LRP on macrophages results in increased [Ca2+]i and inositol 1,4,5-triphosphate [13].
  • To investigate the intracellular pathway of the LRP signaling involved in neurite outgrowth, we tested the effects of alpha2M* on the phosphorylation of the mitogen-activated protein (MAP) extracellular signal-regulated kinases 1 and 2 (ERK1/2) [14].
  • Cs complexes do not stimulate neutrophil or monocytic chemotaxis but are removed by LRP, further underscoring its role as a serpin-enzyme complex clearance receptor [15].

Associations of Mvp with chemical compounds

  • In addition, MVP wild-type and deficient mice were treated with the anthracycline doxorubicin [1].
  • Furthermore, treatment with trichostatin A (TSA), a more specific inhibitor of HDAC, caused an increase in MVP protein, mRNA, and promoter activity [12].
  • The endocytic receptor protein LRP also mediates neuronal calcium signaling via N-methyl-D-aspartate receptors [16].
  • SECs were also degraded by HepG2 cells, and this process was inhibited by LRP antibodies, RAP, and chloroquine [17].
  • These studies are the first to identify a putative binding site in a serine protease inhibitor that is required for LRP-mediated internalization [18].

Other interactions of Mvp

  • To confirm a direct relation between vaults and multidrug resistance, and to investigate other possible functions of vaults, we have generated a major vault protein (MVP/lung resistance-related protein) knockout mouse model [1].

Analytical, diagnostic and therapeutic context of Mvp

  • Immunoprecipitation experiments corroborated these results showing co-precipitation of MVP and beta-tubulin [10].
  • Cryoelectron microscopy imaging of recombinant and tissue derived vaults: localization of the MVP N termini and VPARP [19].
  • To inhibit LRP, the 39-kD protein, which is a potent inhibitor of LRP activity, was overexpressed in the liver of mice using an adenoviral gene transfer technique [8].
  • The cell culture and in vivo experiments revealed that HSPGs are also involved in another, LRP-independent pathway of fVIII catabolism [20].
  • By immunoblotting of CNBr-digested LRP it is shown that Fab A8 binds to a fragment that harbors the second cluster of cysteine-rich complement-type repeats flanked by epidermal growth factor repeats [21].


  1. Disruption of the murine major vault protein (MVP/LRP) gene does not induce hypersensitivity to cytostatics. Mossink, M.H., van Zon, A., Fränzel-Luiten, E., Schoester, M., Kickhoefer, V.A., Scheffer, G.L., Scheper, R.J., Sonneveld, P., Wiemer, E.A. Cancer Res. (2002) [Pubmed]
  2. Decreased expression and function of alpha-2 macroglobulin receptor/low density lipoprotein receptor-related protein in photodynamic therapy-resistant mouse tumor cells. Luna, M.C., Ferrario, A., Rucker, N., Gomer, C.J. Cancer Res. (1995) [Pubmed]
  3. Differential recognition of alpha 1-antitrypsin-elastase and alpha 1-antichymotrypsin-cathepsin G complexes by the low density lipoprotein receptor-related protein. Poller, W., Willnow, T.E., Hilpert, J., Herz, J. J. Biol. Chem. (1995) [Pubmed]
  4. Abnormal guanine nucleotide regulatory protein in MVP dysautonomia: evidence from reconstitution of Gs. Davies, A.O., Su, C.J., Balasubramanyam, A., Codina, J., Birnbaumer, L. J. Clin. Endocrinol. Metab. (1991) [Pubmed]
  5. The cytoplasmic domain of the LDL receptor-related protein regulates multiple steps in APP processing. Pietrzik, C.U., Busse, T., Merriam, D.E., Weggen, S., Koo, E.H. EMBO J. (2002) [Pubmed]
  6. LDL receptor-related protein internalizes and degrades uPA-PAI-1 complexes and is essential for embryo implantation. Herz, J., Clouthier, D.E., Hammer, R.E. Cell (1992) [Pubmed]
  7. Delayed catabolism of apoB-48 lipoproteins due to decreased heparan sulfate proteoglycan production in diabetic mice. Ebara, T., Conde, K., Kako, Y., Liu, Y., Xu, Y., Ramakrishnan, R., Goldberg, I.J., Shachter, N.S. J. Clin. Invest. (2000) [Pubmed]
  8. Two receptor systems are involved in the plasma clearance of tissue-type plasminogen activator (t-PA) in vivo. Narita, M., Bu, G., Herz, J., Schwartz, A.L. J. Clin. Invest. (1995) [Pubmed]
  9. The major vault protein is a novel substrate for the tyrosine phosphatase SHP-2 and scaffold protein in epidermal growth factor signaling. Kolli, S., Zito, C.I., Mossink, M.H., Wiemer, E.A., Bennett, A.M. J. Biol. Chem. (2004) [Pubmed]
  10. Vault mobility depends in part on microtubules and vaults can be recruited to the nuclear envelope. van Zon, A., Mossink, M.H., Houtsmuller, A.B., Schoester, M., Scheffer, G.L., Scheper, R.J., Sonneveld, P., Wiemer, E.A. Exp. Cell Res. (2006) [Pubmed]
  11. The genomic sequence of the murine major vault protein and its promoter. Mossink, M., van Zon, A., Fränzel-Luiten, E., Schoester, M., Scheffer, G.L., Scheper, R.J., Sonneveld, P., Wiemer, E.A. Gene (2002) [Pubmed]
  12. Analysis of MVP and VPARP promoters indicates a role for chromatin remodeling in the regulation of MVP. Emre, N., Raval-Fernandes, S., Kickhoefer, V.A., Rome, L.H. Biochim. Biophys. Acta (2004) [Pubmed]
  13. The relationship between low density lipoprotein-related protein/alpha 2-macroglobulin (alpha 2M) receptors and the newly described alpha 2M signaling receptor. Misra, U.K., Chu, C.T., Gawdi, G., Pizzo, S.V. J. Biol. Chem. (1994) [Pubmed]
  14. Apolipoprotein E receptors mediate neurite outgrowth through activation of p44/42 mitogen-activated protein kinase in primary neurons. Qiu, Z., Hyman, B.T., Rebeck, G.W. J. Biol. Chem. (2004) [Pubmed]
  15. C1 inhibitor-C1s complexes are internalized and degraded by the low density lipoprotein receptor-related protein. Storm, D., Herz, J., Trinder, P., Loos, M. J. Biol. Chem. (1997) [Pubmed]
  16. The endocytic receptor protein LRP also mediates neuronal calcium signaling via N-methyl-D-aspartate receptors. Bacskai, B.J., Xia, M.Q., Strickland, D.K., Rebeck, G.W., Hyman, B.T. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  17. Cellular internalization and degradation of antithrombin III-thrombin, heparin cofactor II-thrombin, and alpha 1-antitrypsin-trypsin complexes is mediated by the low density lipoprotein receptor-related protein. Kounnas, M.Z., Church, F.C., Argraves, W.S., Strickland, D.K. J. Biol. Chem. (1996) [Pubmed]
  18. Identification of a binding site in protease nexin I (PN1) required for the receptor mediated internalization of PN1-thrombin complexes. Knauer, M.F., Hawley, S.B., Knauer, D.J. J. Biol. Chem. (1997) [Pubmed]
  19. Cryoelectron microscopy imaging of recombinant and tissue derived vaults: localization of the MVP N termini and VPARP. Mikyas, Y., Makabi, M., Raval-Fernandes, S., Harrington, L., Kickhoefer, V.A., Rome, L.H., Stewart, P.L. J. Mol. Biol. (2004) [Pubmed]
  20. Cell surface heparan sulfate proteoglycans participate in factor VIII catabolism mediated by low density lipoprotein receptor-related protein. Sarafanov, A.G., Ananyeva, N.M., Shima, M., Saenko, E.L. J. Biol. Chem. (2001) [Pubmed]
  21. Analysis of the binding of pro-urokinase and urokinase-plasminogen activator inhibitor-1 complex to the low density lipoprotein receptor-related protein using a Fab fragment selected from a phage-displayed Fab library. Horn, I.R., Moestrup, S.K., van den Berg, B.M., Pannekoek, H., Nielsen, M.S., van Zonneveld, A.J. J. Biol. Chem. (1995) [Pubmed]
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