MVP (major vault protein)

2000-05-01   Franck Vigué 

Laboratoire de Cytogenetique - Service dHematologie Biologique, Hopital Hotel-Dieu - 75181 Paris Cedex 04, France

Identity

HGNC
LOCATION
16p11.2
LOCUSID
ALIAS
LRP,VAULT1
FUSION GENES

DNA/RNA

Transcription

coding sequence, corresponding to full mRNA, is 2840 bp long

Proteins

Description

110 KD protein, 896 amino acids; major cytoplasmic vault protein; vaults are nucleoproteic complexes composed of the MVP associated with two high-molecular weight proteins p240 and p193 which surround a small 140 nucleotides RNA species

Expression

expressed in a variety of human tumor cell lines, the major part being multidrug resistant; expressed also in primary solid tumors, mainly colon carcinoma or ovarian carcinoma, as well as in hematopoietic cancers (myelodysplastic syndrome, acute myeloid or lymphoid leukemia, multiple myeloma); in normal tissues, LRP expression has a wide distribution, with particularly high levels in epithelial cells of the digestive tract

Localisation

cytoplasmic, in the cytosol, with a little fraction (approximately 5%) located in the nuclear membrane and nuclear pores

Function

vault are cytoplasmic organelles which mediate bidirectional nucleocytoplasmic transport of a wide range of substrates, including cytotoxic drugs; vaults would be involved both in vesicule and cytosolic transport of molecules

Homology

104 kD rat MVP

Implicated in

Entity name
implicated in induced multidrug-resistance to anticancer chemotherapy
Disease
it includes resistance to doxorubicin, vinca alkaloids, mitoxantrone and etoposide; the role of LRP by itself in multidrug-resistance is not completely clear because it is only a part of a nucleo-proteic complex involved in macromolecules transport; the introduction and expression of the LRP gene in cells by transfection does not confer a multidrug-resistance phenotype; overexpression of LRP has been associated with poor response to chemotherapy in various types of leukemia and in ovarian carcinoma, however the role of LRP as pronostic factor remains controversial; in multi-resistant cell lines, LRP amplification within a homogeneous staining region is exceptional

Bibliography

Pubmed IDLast YearTitleAuthors
106517232000P-glycoprotein and multidrug resistance-associated protein, but not lung resistance protein, lower the intracellular daunorubicin accumulation in acute myeloid leukaemic cells.Borg AG et al
97134981998Coexpression of multidrug resistance involve proteins: a flow cytometric analysis.Boutonnat J et al
13607041992Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line.Cole SP et al
95929771998P-glycoprotein (PGP), and not lung resistance-related protein (LRP), is a negative prognostic factor in secondary leukemias.Damiani D et al
104996141999Expression of the lung resistance protein predicts poor outcome in patients with multiple myeloma.Filipits M et al
93579651997Expression of the human major vault protein LRP in acute myeloid leukemia.Hart SM et al
87633381996Major vault protein LRP-related multidrug resistance.Izquierdo MA et al
93785361997Increased LRP mRNA expression is associated with the MDR phenotype in intrinsically resistant human cancer cell lines.Laurençot CM et al
97476351998Multidrug resistance in leukemia.Leith C et al
96435681998Expression of lung resistance protein and correlation with other drug resistance proteins and outcome in myelodysplastic syndromes.Lepelley P et al
105628141999Increased expression of multidrug resistance related proteins Pgp, MRP1, and LRP/MVP occurs early in colorectal carcinogenesis.Meijer GA et al
106975091999Expression of the lung resistance protein (LRP) in primary breast cancer.Pohl G et al
94466661998Lung-resistance-related protein expression is a negative predictive factor for response to conventional low but not to intensified dose alkylating chemotherapy in multiple myeloma.Raaijmakers HG et al
76712231995The LRP gene encoding a major vault protein associated with drug resistance maps proximal to MRP on chromosome 16: evidence that chromosome breakage plays a key role in MRP or LRP gene amplification.Slovak ML et al
97134851998Multidrug resistance and its reversal.Volm M et al
94906951998Relationship between major vault protein/lung resistance protein, multidrug resistance-associated protein, P-glycoprotein expression, and drug resistance in childhood leukemia.den Boer ML et al

Other Information

Locus ID:

NCBI: 9961
MIM: 605088
HGNC: 7531
Ensembl: ENSG00000013364

Variants:

dbSNP: 9961
ClinVar: 9961
TCGA: ENSG00000013364
COSMIC: MVP

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000013364ENST00000357402Q14764
ENSG00000013364ENST00000357402X5D2M8
ENSG00000013364ENST00000395353Q14764
ENSG00000013364ENST00000395353X5D2M8
ENSG00000013364ENST00000562463H3BUP3
ENSG00000013364ENST00000563123I3L155
ENSG00000013364ENST00000563558H3BNF6
ENSG00000013364ENST00000563915H3BQK6
ENSG00000013364ENST00000565164H3BNF2
ENSG00000013364ENST00000566066H3BP76
ENSG00000013364ENST00000566252H3BUK7
ENSG00000013364ENST00000566859H3BQE7
ENSG00000013364ENST00000569887H3BPZ2
ENSG00000013364ENST00000570234H3BRL2
ENSG00000013364ENST00000629059H3BPZ2

Expression (GTEx)

0
50
100
150
200

Pathways

PathwaySourceExternal ID
Immune SystemREACTOMER-HSA-168256
Innate Immune SystemREACTOMER-HSA-168249
Neutrophil degranulationREACTOMER-HSA-6798695

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
282115082017MVP-mediated exosomal sorting of miR-193a promotes colon cancer progression.77
218293652011Recruitment of the major vault protein by InlK: a Listeria monocytogenes strategy to avoid autophagy.72
125764562003RNA expression of breast cancer resistance protein, lung resistance-related protein, multidrug resistance-associated proteins 1 and 2, and multidrug resistance gene 1 in breast cancer: correlation with chemotherapeutic response.69
151330372004The major vault protein is a novel substrate for the tyrosine phosphatase SHP-2 and scaffold protein in epidermal growth factor signaling.50
176153612007Host resistance to lung infection mediated by major vault protein in epithelial cells.41
121770062002PTEN associates with the vault particles in HeLa cells.37
119869442002Increased expression of the breast cancer resistance protein (BCRP) in relapsed or refractory acute myeloid leukemia (AML).34
178755332007Expression of multidrug resistance 1 (MDR1), multidrug resistance-related protein 1 (MRP1), lung resistance protein (LRP), and breast cancer resistance protein (BCRP) genes and clinical outcome in childhood acute lymphoblastic leukemia.27
171788622006Nuclear localization of PTEN is regulated by Ca(2+) through a tyrosil phosphorylation-independent conformational modification in major vault protein.26
198751922010Association of expression of MRP1, BCRP, LRP and ERCC1 with outcome of patients with locally advanced non-small cell lung cancer who received neoadjuvant chemotherapy.20

Citation

Franck Vigué

MVP (major vault protein)

Atlas Genet Cytogenet Oncol Haematol. 2000-05-01

Online version: http://atlasgeneticsoncology.org/gene/120/lrpid120