Full text data of MVP
MVP
(LRP)
[Confidence: low (only semi-automatic identification from reviews)]
Major vault protein; MVP (Lung resistance-related protein)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Major vault protein; MVP (Lung resistance-related protein)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q14764
ID MVP_HUMAN Reviewed; 893 AA.
AC Q14764; Q96BG4; Q9BPW6; Q9BQT1; Q9UBD1;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 4.
DT 22-JAN-2014, entry version 126.
DE RecName: Full=Major vault protein;
DE Short=MVP;
DE AltName: Full=Lung resistance-related protein;
GN Name=MVP; Synonyms=LRP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7585126; DOI=10.1038/nm0695-578;
RA Scheffer G.L., Wijngaard P.L.J., Flens M.J., Izquierdo M.A.,
RA Slovak M.L., Pinedo H.M., Meijer C.J.L.M., Clevers H.C., Scheper R.J.;
RT "The drug resistance-related protein LRP is the human major vault
RT protein.";
RL Nat. Med. 1:578-582(1995).
RN [2]
RP SEQUENCE REVISION TO C-TERMINUS.
RA Scheffer G.L.;
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-169.
RX PubMed=11071864; DOI=10.1006/bbrc.2000.3782;
RA Lange C., Walther W., Schwabe H., Stein U.;
RT "Cloning and initial analysis of the human multidrug resistance-
RT related MVP/LRP gene promoter.";
RL Biochem. Biophys. Res. Commun. 278:125-133(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 1-65.
RC TISSUE=Lung cancer;
RX PubMed=11297743; DOI=10.1016/S0014-5793(01)02318-3;
RA Holzmann K., Ambrosch I., Elbling L., Micksche M., Berger W.;
RT "A small upstream open reading frame causes inhibition of human major
RT vault protein expression from a ubiquitous mRNA splice variant.";
RL FEBS Lett. 494:99-104(2001).
RN [6]
RP PROTEIN SEQUENCE OF 2-9; 68-82 AND 462-474, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RA Quadroni M., Potts A., Barblan J., Bienvenut W.V.;
RL Submitted (JAN-2005) to UniProtKB.
RN [7]
RP ASSOCIATION WITH TEP1.
RX PubMed=10551828; DOI=10.1074/jbc.274.46.32712;
RA Kickhoefer V.A., Stephen A.G., Harrington L., Robinson M.O.,
RA Rome L.H.;
RT "Vaults and telomerase share a common subunit, TEP1.";
RL J. Biol. Chem. 274:32712-32717(1999).
RN [8]
RP INTERACTION WITH PTEN.
RX PubMed=12177006; DOI=10.1074/jbc.M207608200;
RA Yu Z., Fotouhi-Ardakani N., Wu L., Maoui M., Wang S., Banville D.,
RA Shen S.-H.;
RT "PTEN associates with the vault particles in HeLa cells.";
RL J. Biol. Chem. 277:40247-40252(2002).
RN [9]
RP PHOSPHORYLATION AT TYROSINE RESIDUES, MASS SPECTROMETRY, INTERACTION
RP WITH PTPN11, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=15133037; DOI=10.1074/jbc.M313955200;
RA Kolli S., Zito C.I., Mossink M.H., Wiemer E.A.C., Bennett A.M.;
RT "The major vault protein is a novel substrate for the tyrosine
RT phosphatase SHP-2 and scaffold protein in epidermal growth factor
RT signaling.";
RL J. Biol. Chem. 279:29374-29385(2004).
RN [10]
RP INTERACTION WITH ZNF540.
RX PubMed=16815308; DOI=10.1016/j.bbrc.2006.06.076;
RA Xiang Z., Yuan W., Luo N., Wang Y., Tan K., Deng Y., Zhou X., Zhu C.,
RA Li Y., Liu M., Wu X., Li Y.;
RT "A novel human zinc finger protein ZNF540 interacts with MVP and
RT inhibits transcriptional activities of the ERK signal pathway.";
RL Biochem. Biophys. Res. Commun. 347:288-296(2006).
RN [11]
RP FUNCTION, INTERACTION WITH SRC, TYROSINE PHOSPHORYLATION, SUBCELLULAR
RP LOCATION, AND MASS SPECTROMETRY.
RX PubMed=16441665; DOI=10.1111/j.1742-4658.2006.05112.x;
RA Kim E., Lee S., Mian M.F., Yun S.U., Song M., Yi K.-S., Ryu S.H.,
RA Suh P.-G.;
RT "Crosstalk between Src and major vault protein in epidermal growth
RT factor-dependent cell signalling.";
RL FEBS J. 273:793-804(2006).
RN [12]
RP INDUCTION, AND FUNCTION.
RX PubMed=16418217; DOI=10.1242/jcs.02773;
RA Steiner E., Holzmann K., Pirker C., Elbling L., Micksche M.,
RA Sutterluety H., Berger W.;
RT "The major vault protein is responsive to and interferes with
RT interferon-gamma-mediated STAT1 signals.";
RL J. Cell Sci. 119:459-469(2006).
RN [13]
RP INTERACTION WITH APEX1.
RX PubMed=18809583; DOI=10.1128/MCB.00244-08;
RA Chattopadhyay R., Das S., Maiti A.K., Boldogh I., Xie J., Hazra T.K.,
RA Kohno K., Mitra S., Bhakat K.K.;
RT "Regulatory role of human AP-endonuclease (APE1/Ref-1) in YB-1-
RT mediated activation of the multidrug resistance gene MDR1.";
RL Mol. Cell. Biol. 28:7066-7080(2008).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [17]
RP STRUCTURE BY NMR OF 113-221, AND INTERACTION WITH PARP4.
RX PubMed=16373071; DOI=10.1016/j.jmb.2005.11.064;
RA Kozlov G., Vavelyuk O., Minailiuc O., Banville D., Gehring K.,
RA Ekiel I.;
RT "Solution structure of a two-repeat fragment of major vault protein.";
RL J. Mol. Biol. 356:444-452(2006).
CC -!- FUNCTION: Required for normal vault structure. Vaults are multi-
CC subunit structures that may act as scaffolds for proteins involved
CC in signal transduction. Vaults may also play a role in nucleo-
CC cytoplasmic transport. Down-regulates INFG-mediated STAT1
CC signaling and subsequent activation of JAK. Down-regulates SRC
CC activity and signaling through MAP kinases.
CC -!- SUBUNIT: The vault ribonucleoprotein particle is a huge (400 A x
CC 670 A) cage structure of 12.9 MDa. It consists of a dimer of half-
CC vaults, with each half-vault comprising 39 identical major vault
CC protein (MVP) chains, PARP4 and one or more vault RNAs (vRNAs).
CC Interacts with TEP1. Interacts with PTEN and activated MAPK1. The
CC phosphorylated protein interacts with the SH2 domains of PTPN11
CC and SRC. Interacts with APEX1. May interact with ZNF540.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus, nuclear pore complex.
CC Note=5% found in the nuclear pore complex. Translocates from the
CC nucleus to the cytoplasm upon EGF treatment.
CC -!- TISSUE SPECIFICITY: Present in most normal tissues. Higher
CC expression observed in epithelial cells with secretory and
CC excretory functions, as well as in cells chronically exposed to
CC xenobiotics, such as bronchial cells and cells lining the
CC intestine. Overexpressed in many multidrug-resistant cancer cells.
CC -!- INDUCTION: Up-regulated by IFNG/IFN-gamma.
CC -!- DOMAIN: MVP 3 mediates interaction with PTEN.
CC -!- DOMAIN: MVP 4 mediates interaction with PARP4.
CC -!- PTM: Phosphorylated on Tyr residues after EGF stimulation.
CC -!- PTM: Dephosphorylated by PTPN11.
CC -!- SIMILARITY: Contains 9 MVP (vault) repeats.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/LRPID120.html";
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DR EMBL; X79882; CAA56256.2; -; mRNA.
DR EMBL; BC015623; AAH15623.1; -; mRNA.
DR EMBL; AJ238512; CAB55354.1; -; Genomic_DNA.
DR EMBL; AJ238514; CAB55354.1; JOINED; Genomic_DNA.
DR EMBL; AJ238516; CAB55354.1; JOINED; Genomic_DNA.
DR EMBL; AJ238518; CAB55354.1; JOINED; Genomic_DNA.
DR EMBL; AJ238519; CAB55355.1; -; Genomic_DNA.
DR EMBL; AJ238514; CAB55355.1; JOINED; Genomic_DNA.
DR EMBL; AJ238516; CAB55355.1; JOINED; Genomic_DNA.
DR EMBL; AJ238518; CAB55355.1; JOINED; Genomic_DNA.
DR EMBL; AJ291365; CAC35313.1; -; Genomic_DNA.
DR EMBL; AJ291366; CAC35314.1; -; mRNA.
DR EMBL; AJ291367; CAC35316.1; -; mRNA.
DR PIR; S57723; S57723.
DR RefSeq; NP_005106.2; NM_005115.4.
DR RefSeq; NP_059447.2; NM_017458.3.
DR UniGene; Hs.632177; -.
DR PDB; 1Y7X; NMR; -; A=113-221.
DR PDBsum; 1Y7X; -.
DR ProteinModelPortal; Q14764; -.
DR SMR; Q14764; 1-815.
DR IntAct; Q14764; 17.
DR MINT; MINT-5004583; -.
DR STRING; 9606.ENSP00000349977; -.
DR PhosphoSite; Q14764; -.
DR DMDM; 21542417; -.
DR OGP; Q14764; -.
DR REPRODUCTION-2DPAGE; IPI00000105; -.
DR PaxDb; Q14764; -.
DR PeptideAtlas; Q14764; -.
DR PRIDE; Q14764; -.
DR DNASU; 9961; -.
DR Ensembl; ENST00000357402; ENSP00000349977; ENSG00000013364.
DR Ensembl; ENST00000395353; ENSP00000378760; ENSG00000013364.
DR GeneID; 9961; -.
DR KEGG; hsa:9961; -.
DR UCSC; uc002dui.3; human.
DR CTD; 9961; -.
DR GeneCards; GC16P029831; -.
DR HGNC; HGNC:7531; MVP.
DR HPA; CAB002752; -.
DR HPA; CAB022717; -.
DR HPA; HPA002321; -.
DR MIM; 605088; gene.
DR neXtProt; NX_Q14764; -.
DR PharmGKB; PA31332; -.
DR eggNOG; NOG70525; -.
DR HOGENOM; HOG000255109; -.
DR HOVERGEN; HBG003499; -.
DR InParanoid; Q14764; -.
DR KO; K17266; -.
DR OMA; QDPLADR; -.
DR OrthoDB; EOG773XFB; -.
DR PhylomeDB; Q14764; -.
DR SignaLink; Q14764; -.
DR EvolutionaryTrace; Q14764; -.
DR GeneWiki; Major_vault_protein; -.
DR GenomeRNAi; 9961; -.
DR NextBio; 37586; -.
DR PRO; PR:Q14764; -.
DR ArrayExpress; Q14764; -.
DR Bgee; Q14764; -.
DR CleanEx; HS_MVP; -.
DR Genevestigator; Q14764; -.
DR GO; GO:0005856; C:cytoskeleton; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
DR GO; GO:0005643; C:nuclear pore; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0030529; C:ribonucleoprotein complex; IEA:UniProtKB-KW.
DR GO; GO:0019903; F:protein phosphatase binding; IDA:UniProtKB.
DR GO; GO:0008283; P:cell proliferation; IEA:Ensembl.
DR GO; GO:0038127; P:ERBB signaling pathway; IDA:UniProtKB.
DR GO; GO:0051028; P:mRNA transport; IEA:UniProtKB-KW.
DR GO; GO:0031953; P:negative regulation of protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0061099; P:negative regulation of protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0023057; P:negative regulation of signaling; IDA:UniProtKB.
DR GO; GO:0072376; P:protein activation cascade; IEA:Ensembl.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR InterPro; IPR021870; MVP_shoulder.
DR InterPro; IPR002499; Vault_N.
DR Pfam; PF11978; MVP_shoulder; 1.
DR Pfam; PF01505; Vault; 5.
DR PROSITE; PS51224; MVP; 8.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cytoplasm;
KW Direct protein sequencing; mRNA transport; Nuclear pore complex;
KW Nucleus; Phosphoprotein; Polymorphism; Protein transport;
KW Reference proteome; Repeat; Ribonucleoprotein; Translocation;
KW Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 893 Major vault protein.
FT /FTId=PRO_0000158980.
FT REPEAT 2 56 MVP 1.
FT REPEAT 57 111 MVP 2.
FT REPEAT 112 164 MVP 3.
FT REPEAT 165 217 MVP 4.
FT REPEAT 218 272 MVP 5.
FT REPEAT 273 323 MVP 6.
FT REPEAT 324 379 MVP 7.
FT REPEAT 380 457 MVP 8.
FT REPEAT 458 520 MVP 9.
FT MOD_RES 2 2 N-acetylalanine.
FT VARIANT 635 635 V -> I (in dbSNP:rs35916172).
FT /FTId=VAR_050179.
FT VARIANT 651 651 R -> Q (in dbSNP:rs3764944).
FT /FTId=VAR_050180.
FT STRAND 120 125
FT STRAND 137 139
FT STRAND 141 147
FT HELIX 148 150
FT STRAND 157 163
FT STRAND 170 181
FT STRAND 185 187
FT STRAND 195 198
FT STRAND 208 217
SQ SEQUENCE 893 AA; 99327 MW; 6FEE5545B0A3FE65 CRC64;
MATEEFIIRI PPYHYIHVLD QNSNVSRVEV GPKTYIRQDN ERVLFAPMRM VTVPPRHYCT
VANPVSRDAQ GLVLFDVTGQ VRLRHADLEI RLAQDPFPLY PGEVLEKDIT PLQVVLPNTA
LHLKALLDFE DKDGDKVVAG DEWLFEGPGT YIPRKEVEVV EIIQATIIRQ NQALRLRARK
ECWDRDGKER VTGEEWLVTT VGAYLPAVFE EVLDLVDAVI LTEKTALHLR ARRNFRDFRG
VSRRTGEEWL VTVQDTEAHV PDVHEEVLGV VPITTLGPHN YCVILDPVGP DGKNQLGQKR
VVKGEKSFFL QPGEQLEQGI QDVYVLSEQQ GLLLRALQPL EEGEDEEKVS HQAGDHWLIR
GPLEYVPSAK VEVVEERQAI PLDENEGIYV QDVKTGKVRA VIGSTYMLTQ DEVLWEKELP
PGVEELLNKG QDPLADRGEK DTAKSLQPLA PRNKTRVVSY RVPHNAAVQV YDYREKRARV
VFGPELVSLG PEEQFTVLSL SAGRPKRPHA RRALCLLLGP DFFTDVITIE TADHARLQLQ
LAYNWHFEVN DRKDPQETAK LFSVPDFVGD ACKAIASRVR GAVASVTFDD FHKNSARIIR
TAVFGFETSE AKGPDGMALP RPRDQAVFPQ NGLVVSSVDV QSVEPVDQRT RDALQRSVQL
AIEITTNSQE AAAKHEAQRL EQEARGRLER QKILDQSEAE KARKELLELE ALSMAVESTG
TAKAEAESRA EAARIEGEGS VLQAKLKAQA LAIETEAELQ RVQKVRELEL VYARAQLELE
VSKAQQLAEV EVKKFKQMTE AIGPSTIRDL AVAGPEMQVK LLQSLGLKST LITDGSTPIN
LFNTAFGLLG MGPEGQPLGR RVASGPSPGE GISPQSAQAP QAPGDNHVVP VLR
//
ID MVP_HUMAN Reviewed; 893 AA.
AC Q14764; Q96BG4; Q9BPW6; Q9BQT1; Q9UBD1;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 4.
DT 22-JAN-2014, entry version 126.
DE RecName: Full=Major vault protein;
DE Short=MVP;
DE AltName: Full=Lung resistance-related protein;
GN Name=MVP; Synonyms=LRP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7585126; DOI=10.1038/nm0695-578;
RA Scheffer G.L., Wijngaard P.L.J., Flens M.J., Izquierdo M.A.,
RA Slovak M.L., Pinedo H.M., Meijer C.J.L.M., Clevers H.C., Scheper R.J.;
RT "The drug resistance-related protein LRP is the human major vault
RT protein.";
RL Nat. Med. 1:578-582(1995).
RN [2]
RP SEQUENCE REVISION TO C-TERMINUS.
RA Scheffer G.L.;
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-169.
RX PubMed=11071864; DOI=10.1006/bbrc.2000.3782;
RA Lange C., Walther W., Schwabe H., Stein U.;
RT "Cloning and initial analysis of the human multidrug resistance-
RT related MVP/LRP gene promoter.";
RL Biochem. Biophys. Res. Commun. 278:125-133(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 1-65.
RC TISSUE=Lung cancer;
RX PubMed=11297743; DOI=10.1016/S0014-5793(01)02318-3;
RA Holzmann K., Ambrosch I., Elbling L., Micksche M., Berger W.;
RT "A small upstream open reading frame causes inhibition of human major
RT vault protein expression from a ubiquitous mRNA splice variant.";
RL FEBS Lett. 494:99-104(2001).
RN [6]
RP PROTEIN SEQUENCE OF 2-9; 68-82 AND 462-474, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RA Quadroni M., Potts A., Barblan J., Bienvenut W.V.;
RL Submitted (JAN-2005) to UniProtKB.
RN [7]
RP ASSOCIATION WITH TEP1.
RX PubMed=10551828; DOI=10.1074/jbc.274.46.32712;
RA Kickhoefer V.A., Stephen A.G., Harrington L., Robinson M.O.,
RA Rome L.H.;
RT "Vaults and telomerase share a common subunit, TEP1.";
RL J. Biol. Chem. 274:32712-32717(1999).
RN [8]
RP INTERACTION WITH PTEN.
RX PubMed=12177006; DOI=10.1074/jbc.M207608200;
RA Yu Z., Fotouhi-Ardakani N., Wu L., Maoui M., Wang S., Banville D.,
RA Shen S.-H.;
RT "PTEN associates with the vault particles in HeLa cells.";
RL J. Biol. Chem. 277:40247-40252(2002).
RN [9]
RP PHOSPHORYLATION AT TYROSINE RESIDUES, MASS SPECTROMETRY, INTERACTION
RP WITH PTPN11, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=15133037; DOI=10.1074/jbc.M313955200;
RA Kolli S., Zito C.I., Mossink M.H., Wiemer E.A.C., Bennett A.M.;
RT "The major vault protein is a novel substrate for the tyrosine
RT phosphatase SHP-2 and scaffold protein in epidermal growth factor
RT signaling.";
RL J. Biol. Chem. 279:29374-29385(2004).
RN [10]
RP INTERACTION WITH ZNF540.
RX PubMed=16815308; DOI=10.1016/j.bbrc.2006.06.076;
RA Xiang Z., Yuan W., Luo N., Wang Y., Tan K., Deng Y., Zhou X., Zhu C.,
RA Li Y., Liu M., Wu X., Li Y.;
RT "A novel human zinc finger protein ZNF540 interacts with MVP and
RT inhibits transcriptional activities of the ERK signal pathway.";
RL Biochem. Biophys. Res. Commun. 347:288-296(2006).
RN [11]
RP FUNCTION, INTERACTION WITH SRC, TYROSINE PHOSPHORYLATION, SUBCELLULAR
RP LOCATION, AND MASS SPECTROMETRY.
RX PubMed=16441665; DOI=10.1111/j.1742-4658.2006.05112.x;
RA Kim E., Lee S., Mian M.F., Yun S.U., Song M., Yi K.-S., Ryu S.H.,
RA Suh P.-G.;
RT "Crosstalk between Src and major vault protein in epidermal growth
RT factor-dependent cell signalling.";
RL FEBS J. 273:793-804(2006).
RN [12]
RP INDUCTION, AND FUNCTION.
RX PubMed=16418217; DOI=10.1242/jcs.02773;
RA Steiner E., Holzmann K., Pirker C., Elbling L., Micksche M.,
RA Sutterluety H., Berger W.;
RT "The major vault protein is responsive to and interferes with
RT interferon-gamma-mediated STAT1 signals.";
RL J. Cell Sci. 119:459-469(2006).
RN [13]
RP INTERACTION WITH APEX1.
RX PubMed=18809583; DOI=10.1128/MCB.00244-08;
RA Chattopadhyay R., Das S., Maiti A.K., Boldogh I., Xie J., Hazra T.K.,
RA Kohno K., Mitra S., Bhakat K.K.;
RT "Regulatory role of human AP-endonuclease (APE1/Ref-1) in YB-1-
RT mediated activation of the multidrug resistance gene MDR1.";
RL Mol. Cell. Biol. 28:7066-7080(2008).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [17]
RP STRUCTURE BY NMR OF 113-221, AND INTERACTION WITH PARP4.
RX PubMed=16373071; DOI=10.1016/j.jmb.2005.11.064;
RA Kozlov G., Vavelyuk O., Minailiuc O., Banville D., Gehring K.,
RA Ekiel I.;
RT "Solution structure of a two-repeat fragment of major vault protein.";
RL J. Mol. Biol. 356:444-452(2006).
CC -!- FUNCTION: Required for normal vault structure. Vaults are multi-
CC subunit structures that may act as scaffolds for proteins involved
CC in signal transduction. Vaults may also play a role in nucleo-
CC cytoplasmic transport. Down-regulates INFG-mediated STAT1
CC signaling and subsequent activation of JAK. Down-regulates SRC
CC activity and signaling through MAP kinases.
CC -!- SUBUNIT: The vault ribonucleoprotein particle is a huge (400 A x
CC 670 A) cage structure of 12.9 MDa. It consists of a dimer of half-
CC vaults, with each half-vault comprising 39 identical major vault
CC protein (MVP) chains, PARP4 and one or more vault RNAs (vRNAs).
CC Interacts with TEP1. Interacts with PTEN and activated MAPK1. The
CC phosphorylated protein interacts with the SH2 domains of PTPN11
CC and SRC. Interacts with APEX1. May interact with ZNF540.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus, nuclear pore complex.
CC Note=5% found in the nuclear pore complex. Translocates from the
CC nucleus to the cytoplasm upon EGF treatment.
CC -!- TISSUE SPECIFICITY: Present in most normal tissues. Higher
CC expression observed in epithelial cells with secretory and
CC excretory functions, as well as in cells chronically exposed to
CC xenobiotics, such as bronchial cells and cells lining the
CC intestine. Overexpressed in many multidrug-resistant cancer cells.
CC -!- INDUCTION: Up-regulated by IFNG/IFN-gamma.
CC -!- DOMAIN: MVP 3 mediates interaction with PTEN.
CC -!- DOMAIN: MVP 4 mediates interaction with PARP4.
CC -!- PTM: Phosphorylated on Tyr residues after EGF stimulation.
CC -!- PTM: Dephosphorylated by PTPN11.
CC -!- SIMILARITY: Contains 9 MVP (vault) repeats.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/LRPID120.html";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; X79882; CAA56256.2; -; mRNA.
DR EMBL; BC015623; AAH15623.1; -; mRNA.
DR EMBL; AJ238512; CAB55354.1; -; Genomic_DNA.
DR EMBL; AJ238514; CAB55354.1; JOINED; Genomic_DNA.
DR EMBL; AJ238516; CAB55354.1; JOINED; Genomic_DNA.
DR EMBL; AJ238518; CAB55354.1; JOINED; Genomic_DNA.
DR EMBL; AJ238519; CAB55355.1; -; Genomic_DNA.
DR EMBL; AJ238514; CAB55355.1; JOINED; Genomic_DNA.
DR EMBL; AJ238516; CAB55355.1; JOINED; Genomic_DNA.
DR EMBL; AJ238518; CAB55355.1; JOINED; Genomic_DNA.
DR EMBL; AJ291365; CAC35313.1; -; Genomic_DNA.
DR EMBL; AJ291366; CAC35314.1; -; mRNA.
DR EMBL; AJ291367; CAC35316.1; -; mRNA.
DR PIR; S57723; S57723.
DR RefSeq; NP_005106.2; NM_005115.4.
DR RefSeq; NP_059447.2; NM_017458.3.
DR UniGene; Hs.632177; -.
DR PDB; 1Y7X; NMR; -; A=113-221.
DR PDBsum; 1Y7X; -.
DR ProteinModelPortal; Q14764; -.
DR SMR; Q14764; 1-815.
DR IntAct; Q14764; 17.
DR MINT; MINT-5004583; -.
DR STRING; 9606.ENSP00000349977; -.
DR PhosphoSite; Q14764; -.
DR DMDM; 21542417; -.
DR OGP; Q14764; -.
DR REPRODUCTION-2DPAGE; IPI00000105; -.
DR PaxDb; Q14764; -.
DR PeptideAtlas; Q14764; -.
DR PRIDE; Q14764; -.
DR DNASU; 9961; -.
DR Ensembl; ENST00000357402; ENSP00000349977; ENSG00000013364.
DR Ensembl; ENST00000395353; ENSP00000378760; ENSG00000013364.
DR GeneID; 9961; -.
DR KEGG; hsa:9961; -.
DR UCSC; uc002dui.3; human.
DR CTD; 9961; -.
DR GeneCards; GC16P029831; -.
DR HGNC; HGNC:7531; MVP.
DR HPA; CAB002752; -.
DR HPA; CAB022717; -.
DR HPA; HPA002321; -.
DR MIM; 605088; gene.
DR neXtProt; NX_Q14764; -.
DR PharmGKB; PA31332; -.
DR eggNOG; NOG70525; -.
DR HOGENOM; HOG000255109; -.
DR HOVERGEN; HBG003499; -.
DR InParanoid; Q14764; -.
DR KO; K17266; -.
DR OMA; QDPLADR; -.
DR OrthoDB; EOG773XFB; -.
DR PhylomeDB; Q14764; -.
DR SignaLink; Q14764; -.
DR EvolutionaryTrace; Q14764; -.
DR GeneWiki; Major_vault_protein; -.
DR GenomeRNAi; 9961; -.
DR NextBio; 37586; -.
DR PRO; PR:Q14764; -.
DR ArrayExpress; Q14764; -.
DR Bgee; Q14764; -.
DR CleanEx; HS_MVP; -.
DR Genevestigator; Q14764; -.
DR GO; GO:0005856; C:cytoskeleton; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
DR GO; GO:0005643; C:nuclear pore; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0030529; C:ribonucleoprotein complex; IEA:UniProtKB-KW.
DR GO; GO:0019903; F:protein phosphatase binding; IDA:UniProtKB.
DR GO; GO:0008283; P:cell proliferation; IEA:Ensembl.
DR GO; GO:0038127; P:ERBB signaling pathway; IDA:UniProtKB.
DR GO; GO:0051028; P:mRNA transport; IEA:UniProtKB-KW.
DR GO; GO:0031953; P:negative regulation of protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0061099; P:negative regulation of protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0023057; P:negative regulation of signaling; IDA:UniProtKB.
DR GO; GO:0072376; P:protein activation cascade; IEA:Ensembl.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR InterPro; IPR021870; MVP_shoulder.
DR InterPro; IPR002499; Vault_N.
DR Pfam; PF11978; MVP_shoulder; 1.
DR Pfam; PF01505; Vault; 5.
DR PROSITE; PS51224; MVP; 8.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cytoplasm;
KW Direct protein sequencing; mRNA transport; Nuclear pore complex;
KW Nucleus; Phosphoprotein; Polymorphism; Protein transport;
KW Reference proteome; Repeat; Ribonucleoprotein; Translocation;
KW Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 893 Major vault protein.
FT /FTId=PRO_0000158980.
FT REPEAT 2 56 MVP 1.
FT REPEAT 57 111 MVP 2.
FT REPEAT 112 164 MVP 3.
FT REPEAT 165 217 MVP 4.
FT REPEAT 218 272 MVP 5.
FT REPEAT 273 323 MVP 6.
FT REPEAT 324 379 MVP 7.
FT REPEAT 380 457 MVP 8.
FT REPEAT 458 520 MVP 9.
FT MOD_RES 2 2 N-acetylalanine.
FT VARIANT 635 635 V -> I (in dbSNP:rs35916172).
FT /FTId=VAR_050179.
FT VARIANT 651 651 R -> Q (in dbSNP:rs3764944).
FT /FTId=VAR_050180.
FT STRAND 120 125
FT STRAND 137 139
FT STRAND 141 147
FT HELIX 148 150
FT STRAND 157 163
FT STRAND 170 181
FT STRAND 185 187
FT STRAND 195 198
FT STRAND 208 217
SQ SEQUENCE 893 AA; 99327 MW; 6FEE5545B0A3FE65 CRC64;
MATEEFIIRI PPYHYIHVLD QNSNVSRVEV GPKTYIRQDN ERVLFAPMRM VTVPPRHYCT
VANPVSRDAQ GLVLFDVTGQ VRLRHADLEI RLAQDPFPLY PGEVLEKDIT PLQVVLPNTA
LHLKALLDFE DKDGDKVVAG DEWLFEGPGT YIPRKEVEVV EIIQATIIRQ NQALRLRARK
ECWDRDGKER VTGEEWLVTT VGAYLPAVFE EVLDLVDAVI LTEKTALHLR ARRNFRDFRG
VSRRTGEEWL VTVQDTEAHV PDVHEEVLGV VPITTLGPHN YCVILDPVGP DGKNQLGQKR
VVKGEKSFFL QPGEQLEQGI QDVYVLSEQQ GLLLRALQPL EEGEDEEKVS HQAGDHWLIR
GPLEYVPSAK VEVVEERQAI PLDENEGIYV QDVKTGKVRA VIGSTYMLTQ DEVLWEKELP
PGVEELLNKG QDPLADRGEK DTAKSLQPLA PRNKTRVVSY RVPHNAAVQV YDYREKRARV
VFGPELVSLG PEEQFTVLSL SAGRPKRPHA RRALCLLLGP DFFTDVITIE TADHARLQLQ
LAYNWHFEVN DRKDPQETAK LFSVPDFVGD ACKAIASRVR GAVASVTFDD FHKNSARIIR
TAVFGFETSE AKGPDGMALP RPRDQAVFPQ NGLVVSSVDV QSVEPVDQRT RDALQRSVQL
AIEITTNSQE AAAKHEAQRL EQEARGRLER QKILDQSEAE KARKELLELE ALSMAVESTG
TAKAEAESRA EAARIEGEGS VLQAKLKAQA LAIETEAELQ RVQKVRELEL VYARAQLELE
VSKAQQLAEV EVKKFKQMTE AIGPSTIRDL AVAGPEMQVK LLQSLGLKST LITDGSTPIN
LFNTAFGLLG MGPEGQPLGR RVASGPSPGE GISPQSAQAP QAPGDNHVVP VLR
//
MIM
605088
*RECORD*
*FIELD* NO
605088
*FIELD* TI
*605088 MAJOR VAULT PROTEIN, RAT, HOMOLOG OF; MVP
;;LUNG RESISTANCE-RELATED PROTEIN; LRP
read more*FIELD* TX
DESCRIPTION
Vaults are hollow intracellular organelles with dimensions of about 57
by 32 nm and a nuclear mass of about 13 MD, 3 times the size of a
ribosome. They are composed of a small RNA (VTRNA1-1; 612695), the
100-kD major vault protein (MVP), and minor vault proteins of 193 kD
(PARP4; 607519) and 240 kD (TEP1; 601686). MVP accounts for over 70% of
the particle mass (Izquierdo et al., 1996; Kickhoefer et al., 1999).
CLONING
Multidrug-resistant (MDR) cancer cells frequently overexpress the 110-kD
lung resistance-related protein (LRP). Overexpression of LRP often
predicts a poor response to chemotherapy. By screening a
multidrug-resistant non-P-glycoprotein (see ABCB1; 171050) fibrosarcoma
cell line with an LRP-specific monoclonal antibody, Scheffer et al.
(1995) isolated a cDNA encoding LRP. The deduced 896-amino acid LRP
protein shares 88% amino acid identity with the rat major vault protein
(Mvp). RNase protection assays showed that LRP expression was enhanced
4- to 8-fold in non-P-glycoprotein MDR cell lines.
Using immunohistochemical analysis, Izquierdo et al. (1996) found that
LRP was widely expressed in normal and tumor tissues and showed a
characteristic cytoplasmic granular pattern. High LRP expression was
detected in the epithelial lining of bronchioles and upper and lower
digestive tract, renal proximal tubules, epidermal keratinocytes and
melanocytes, macrophages, and adrenal cortex. Lower and variable
expression of LRP was detected in other tissues. LRP was expressed in
all tumor types tested, and its level of expression fairly reflected the
chemosensitivity of the tumors, with lower expression in highly
chemosensitive tumors. Immunoprecipitated LRP had an apparent molecular
mass of 110 kD by SDS-PAGE.
By EST database analysis, Holzmann et al. (2001) identified a long MVP
splice variant, L-MVP, that contains a 41-bp stretch in the 5-prime
region that is intronic in the shorter S-MVP splice variant. This 41-bp
stretch introduces an upstream ORF encoding a deduced 18-amino acid
peptide. RT-PCR detected ubiquitous expression of both variants, and
S-MVP was always the major variant.
Van Zon et al. (2002) identified a central calcium-binding EF-hand motif
and a C-terminal coiled-coil domain in MVP.
Using confocal immunocytochemistry with anti-MVP antibody, Slesina et
al. (2005) found a dense distribution of vault particles in the
cytoplasm of human U373 astroglioma cell line. A punctate staining
pattern was also detected in the nucleus. Cryoimmunoelectron microscopy
revealed clusters of immunogold particles at nuclear pores and in the
nucleoplasm, suggesting that nuclear MVP was also associated with
vaults. Quantification of fluorescent MVP in the cytosol and nucleus of
U373 cells revealed about 5% of MVP in the nucleus.
GENE FUNCTION
Kickhoefer et al. (1998) found that expression of MVP and VTRNA1-1 and
assembly of vaults increased up to 15-fold in several drug-resistant
cell lines compared with the parental cell lines. They hypothesized that
the absolute vault level in cell lines may dictate the extent of drug
resistance.
Abbondanza et al. (1998) found that MVP coprecipitated with estrogen
receptor (ER, or ESR1; 133430) from nuclear extracts of MCF-7 human
breast cancer cells and that ER associated with intact vaults. Mutation
analysis showed that a central region of ER containing nuclear
localization signals was involved in the interaction. A limited amount
of ER molecules in the nuclear extract appeared to be associated with
MVP. Physiologic concentrations of estradiol increased the amount of MVP
present in MCF-7 nuclear extracts and coimmunoprecipitated with ER. The
hormone-dependent interaction of vaults with ER was reproduced in vitro.
Antibodies to progesterone receptor (PGR; 607311) and glucocorticoid
receptor (GCCR; 138040) also coimmunoprecipitated MVP, but more weakly.
By yeast 2-hybrid analysis and by in vitro binding assays with
recombinant proteins, Kickhoefer et al. (1999) confirmed direct
interaction between MVP and PARP4, which they called VPARP. The
C-terminal domain was the smallest sequence of PARP4 that could bind
MVP. The PARP-like catalytic domain, when expressed as a recombinant
protein in E. coli, showed ADP-ribosylase activity. Vault particles
purified from rat liver and incubated with radiolabeled NAD showed
prominent ADP-ribosylation of Mvp and some automodification of Parp4.
Holzmann et al. (2001) showed that in vitro translation of L-MVP was low
relative to translation of S-MVP. Mutation of the start codon of the
upstream ORF in the L-MVP transcript reversed the suppression of MVP
translation, suggesting that translation of the upstream ORF controls
expression of the larger protein.
Using yeast 2- and 3-hybrid analysis and mutation analysis, van Zon et
al. (2002) found that MVP molecules interacted with each other via their
coiled-coil domains. MVP also bound calcium, likely via its EF-hand
motif. The N-terminal half of MVP bound a C-terminal domain of VPARP,
but TEP1 did not appear to interact with either MVP or VPARP.
Using a yeast 2-hybrid screen, Yu et al. (2002) showed that MPV
interacted with PTEN (601728), a protein phosphatase that can function
as a tumor suppressor. Endogenous PTEN associated with vault particles
isolated from HeLa cells. Coimmunoprecipitation analysis confirmed the
interaction between PTEN and MVP. Deletion analysis mapped the
interacting regions to the C2 domain of PTEN and the EF-hand motifs of
MVP. The interaction was independent of tyrosine phosphorylation, but
required calcium, consistent with a calcium-induced conformational
change in the MVP EF-hand motifs.
Using human airway epithelial cells, Kowalski et al. (2007) showed that
MVP accumulated rapidly into lipid rafts during Pseudomonas aeruginosa
infection, and this accumulation was markedly reduced in cells from
cystic fibrosis (219700) patients expressing the delF508 mutation
(602421.0001) in CFTR (602421). Immunofluorescence microscopy and
coimmunoprecipitation experiments demonstrated colocalization of
bacteria, CFTR, and MVP, without direct physical association. The outer
core oligosaccharide of P. aeruginosa bound CFTR and was required for
recruitment of MVP to lipid rafts. Small interfering RNA-mediated
knockdown of MVP decreased recruitment of MVP to lipid rafts following
P. aeruginosa infection without affecting NFKB (see 164011) activation,
IL8 (146930) secretion, or apoptosis induction, suggesting a key role
for MVP in bacterial uptake.
GENE STRUCTURE
Lange et al. (2000) determined that the MVP gene contains 15 exons. They
found that the promoter region has an inverted CCAAT box but no TATA
box. They identified several putative promoter binding sites including
an SP1 (189901)-binding site located close to a p53 (191170)-binding
motif. An alternative 3-prime splice site of intron 1 results in a
splicing variant within the 5-prime untranslated region of MVP mRNA.
MAPPING
By FISH, Scheffer et al. (1995) mapped the LRP gene to chromosome
16p13.1-p11.2, in the same chromosomal region as the MDR-associated
genes MRP (ABCC1; 158343) and PRKCB1 (176970). The authors noted that
acute myeloid leukemia patients with a deletion of an MRP gene,
resulting from a chromosome 16 inversion, often have a favorable
outcome.
ANIMAL MODEL
Kowalski et al. (2007) found that Mvp -/- mice infected with P.
aeruginosa internalized fewer bacteria in lung epithelial cells than
wildtype mice, resulting in increased bacterial burden in the lung. Mvp
-/- mice also had increased mortality after P. aeruginosa infection.
Kowalski et al. (2007) concluded that MVP contributes to resistance
against P. aeruginosa lung infection.
*FIELD* RF
1. Abbondanza, C.; Rossi, V.; Roscigno, A.; Gallo, L.; Belsito, A.;
Piluso, G.; Medici, N.; Nigro, V.; Molinari, A. M.; Moncharmont, B.;
Puca, G. A.: Interaction of vault particles with estrogen receptor
in the MCF-7 breast cancer cell. J. Cell Biol. 141: 1301-1310, 1998.
2. Holzmann, K.; Ambrosch, I.; Elbling, L.; Micksche, M.; Berger,
W.: A small upstream open reading frame causes inhibition of human
major vault protein expression from a ubiquitous mRNA splice variant. FEBS
Lett. 494: 99-104, 2001.
3. Izquierdo, M. A.; Scheffer, G. L.; Flens, M. J.; Giaccone, G.;
Broxterman, H. J.; Meijer, C. J. L. M.; van der Valk, P.; Scheper,
R. J.: Broad distribution of the multidrug resistance-related vault
lung resistance protein in normal human tissues and tumors. Am. J.
Path. 148: 877-887, 1996.
4. Kickhoefer, V. A.; Rajavel, K. S.; Scheffer, G. L.; Dalton, W.
S.; Scheper, R. J.; Rome, L. H.: Vaults are up-regulated in multidrug-resistant
cancer cell lines. J. Biol. Chem. 273: 8971-8974, 1998.
5. Kickhoefer, V. A.; Siva, A. C.; Kedersha, N. L.; Inman, E. M.;
Ruland, C.; Streuli, M.; Rome, L. H.: The 193-kD vault protein, VPARP,
is a novel poly(ADP-ribose) polymerase. J. Cell Biol. 146: 917-928,
1999.
6. Kickhoefer, V. A.; Stephen, A. G.; Harrington, L.; Robinson, M.
O.; Rome, L. H.: Vaults and telomerase share a common subunit, TEP1. J.
Biol. Chem. 274: 32712-32717, 1999.
7. Kowalski, M. P.; Dubouix-Bourandy, A.; Bajmoczi, M.; Golan, D.
E.; Zaidi, T.; Coutinho-Sledge, Y. S.; Gygi, M. P.; Gygi, S. P.; Wiemer,
E. A. C.; Pier, G. B.: Host resistance to lung infection mediated
by major vault protein in epithelial cells. Science 317: 130-132,
2007.
8. Lange, C.; Walther, W.; Schwabe, H.; Stein, U.: Cloning and initial
analysis of the human multidrug resistance-related MVP/LRP gene promoter. Biochem.
Biophys. Res. Commun. 278: 125-133, 2000.
9. Scheffer, G. L.; Wijngaard, P. L. J.; Flens, M. J.; Izquierdo,
M. A.; Slovak, M. L.; Pinedo, H. M.; Meijer, C. J. L. M.; Clevers,
H. C.; Scheper, R. J.: The drug resistance-related protein LRP is
the human major vault protein. Nature Med. 1: 578-582, 1995.
10. Slesina, M.; Inman, E. M.; Rome, L. H.; Volknandt, W.: Nuclear
localization of the major vault protein in U373 cells. Cell Tissue
Res. 321: 97-104, 2005.
11. van Zon, A.; Mossink, M. H.; Schoester, M.; Scheffer, G. L.; Scheper,
R. J.; Sonneveld, P.; Wiemer, E. A. C.: Structural domains of vault
proteins: a role for the coiled coil domain in vault assembly. Biochem.
Biophys. Res. Commun. 291: 535-541, 2002.
12. Yu, Z.; Fotouhi-Ardakani, N.; Wu, L.; Maoui, M.; Wang, S.; Banville,
D.; Shen, S.-H.: PTEN associates with the vault particles in HeLa
cells. J. Biol. Chem. 277: 40247-40252, 2002.
*FIELD* CN
Patricia A. Hartz - updated: 3/6/2009
Paul J. Converse - updated: 7/17/2007
Patricia A. Hartz - updated: 7/30/2002
*FIELD* CD
Paul J. Converse: 6/28/2000
*FIELD* ED
mgross: 03/26/2009
terry: 3/6/2009
mgross: 7/18/2007
terry: 7/17/2007
carol: 7/30/2002
mgross: 8/11/2000
mgross: 6/29/2000
mgross: 6/28/2000
*RECORD*
*FIELD* NO
605088
*FIELD* TI
*605088 MAJOR VAULT PROTEIN, RAT, HOMOLOG OF; MVP
;;LUNG RESISTANCE-RELATED PROTEIN; LRP
read more*FIELD* TX
DESCRIPTION
Vaults are hollow intracellular organelles with dimensions of about 57
by 32 nm and a nuclear mass of about 13 MD, 3 times the size of a
ribosome. They are composed of a small RNA (VTRNA1-1; 612695), the
100-kD major vault protein (MVP), and minor vault proteins of 193 kD
(PARP4; 607519) and 240 kD (TEP1; 601686). MVP accounts for over 70% of
the particle mass (Izquierdo et al., 1996; Kickhoefer et al., 1999).
CLONING
Multidrug-resistant (MDR) cancer cells frequently overexpress the 110-kD
lung resistance-related protein (LRP). Overexpression of LRP often
predicts a poor response to chemotherapy. By screening a
multidrug-resistant non-P-glycoprotein (see ABCB1; 171050) fibrosarcoma
cell line with an LRP-specific monoclonal antibody, Scheffer et al.
(1995) isolated a cDNA encoding LRP. The deduced 896-amino acid LRP
protein shares 88% amino acid identity with the rat major vault protein
(Mvp). RNase protection assays showed that LRP expression was enhanced
4- to 8-fold in non-P-glycoprotein MDR cell lines.
Using immunohistochemical analysis, Izquierdo et al. (1996) found that
LRP was widely expressed in normal and tumor tissues and showed a
characteristic cytoplasmic granular pattern. High LRP expression was
detected in the epithelial lining of bronchioles and upper and lower
digestive tract, renal proximal tubules, epidermal keratinocytes and
melanocytes, macrophages, and adrenal cortex. Lower and variable
expression of LRP was detected in other tissues. LRP was expressed in
all tumor types tested, and its level of expression fairly reflected the
chemosensitivity of the tumors, with lower expression in highly
chemosensitive tumors. Immunoprecipitated LRP had an apparent molecular
mass of 110 kD by SDS-PAGE.
By EST database analysis, Holzmann et al. (2001) identified a long MVP
splice variant, L-MVP, that contains a 41-bp stretch in the 5-prime
region that is intronic in the shorter S-MVP splice variant. This 41-bp
stretch introduces an upstream ORF encoding a deduced 18-amino acid
peptide. RT-PCR detected ubiquitous expression of both variants, and
S-MVP was always the major variant.
Van Zon et al. (2002) identified a central calcium-binding EF-hand motif
and a C-terminal coiled-coil domain in MVP.
Using confocal immunocytochemistry with anti-MVP antibody, Slesina et
al. (2005) found a dense distribution of vault particles in the
cytoplasm of human U373 astroglioma cell line. A punctate staining
pattern was also detected in the nucleus. Cryoimmunoelectron microscopy
revealed clusters of immunogold particles at nuclear pores and in the
nucleoplasm, suggesting that nuclear MVP was also associated with
vaults. Quantification of fluorescent MVP in the cytosol and nucleus of
U373 cells revealed about 5% of MVP in the nucleus.
GENE FUNCTION
Kickhoefer et al. (1998) found that expression of MVP and VTRNA1-1 and
assembly of vaults increased up to 15-fold in several drug-resistant
cell lines compared with the parental cell lines. They hypothesized that
the absolute vault level in cell lines may dictate the extent of drug
resistance.
Abbondanza et al. (1998) found that MVP coprecipitated with estrogen
receptor (ER, or ESR1; 133430) from nuclear extracts of MCF-7 human
breast cancer cells and that ER associated with intact vaults. Mutation
analysis showed that a central region of ER containing nuclear
localization signals was involved in the interaction. A limited amount
of ER molecules in the nuclear extract appeared to be associated with
MVP. Physiologic concentrations of estradiol increased the amount of MVP
present in MCF-7 nuclear extracts and coimmunoprecipitated with ER. The
hormone-dependent interaction of vaults with ER was reproduced in vitro.
Antibodies to progesterone receptor (PGR; 607311) and glucocorticoid
receptor (GCCR; 138040) also coimmunoprecipitated MVP, but more weakly.
By yeast 2-hybrid analysis and by in vitro binding assays with
recombinant proteins, Kickhoefer et al. (1999) confirmed direct
interaction between MVP and PARP4, which they called VPARP. The
C-terminal domain was the smallest sequence of PARP4 that could bind
MVP. The PARP-like catalytic domain, when expressed as a recombinant
protein in E. coli, showed ADP-ribosylase activity. Vault particles
purified from rat liver and incubated with radiolabeled NAD showed
prominent ADP-ribosylation of Mvp and some automodification of Parp4.
Holzmann et al. (2001) showed that in vitro translation of L-MVP was low
relative to translation of S-MVP. Mutation of the start codon of the
upstream ORF in the L-MVP transcript reversed the suppression of MVP
translation, suggesting that translation of the upstream ORF controls
expression of the larger protein.
Using yeast 2- and 3-hybrid analysis and mutation analysis, van Zon et
al. (2002) found that MVP molecules interacted with each other via their
coiled-coil domains. MVP also bound calcium, likely via its EF-hand
motif. The N-terminal half of MVP bound a C-terminal domain of VPARP,
but TEP1 did not appear to interact with either MVP or VPARP.
Using a yeast 2-hybrid screen, Yu et al. (2002) showed that MPV
interacted with PTEN (601728), a protein phosphatase that can function
as a tumor suppressor. Endogenous PTEN associated with vault particles
isolated from HeLa cells. Coimmunoprecipitation analysis confirmed the
interaction between PTEN and MVP. Deletion analysis mapped the
interacting regions to the C2 domain of PTEN and the EF-hand motifs of
MVP. The interaction was independent of tyrosine phosphorylation, but
required calcium, consistent with a calcium-induced conformational
change in the MVP EF-hand motifs.
Using human airway epithelial cells, Kowalski et al. (2007) showed that
MVP accumulated rapidly into lipid rafts during Pseudomonas aeruginosa
infection, and this accumulation was markedly reduced in cells from
cystic fibrosis (219700) patients expressing the delF508 mutation
(602421.0001) in CFTR (602421). Immunofluorescence microscopy and
coimmunoprecipitation experiments demonstrated colocalization of
bacteria, CFTR, and MVP, without direct physical association. The outer
core oligosaccharide of P. aeruginosa bound CFTR and was required for
recruitment of MVP to lipid rafts. Small interfering RNA-mediated
knockdown of MVP decreased recruitment of MVP to lipid rafts following
P. aeruginosa infection without affecting NFKB (see 164011) activation,
IL8 (146930) secretion, or apoptosis induction, suggesting a key role
for MVP in bacterial uptake.
GENE STRUCTURE
Lange et al. (2000) determined that the MVP gene contains 15 exons. They
found that the promoter region has an inverted CCAAT box but no TATA
box. They identified several putative promoter binding sites including
an SP1 (189901)-binding site located close to a p53 (191170)-binding
motif. An alternative 3-prime splice site of intron 1 results in a
splicing variant within the 5-prime untranslated region of MVP mRNA.
MAPPING
By FISH, Scheffer et al. (1995) mapped the LRP gene to chromosome
16p13.1-p11.2, in the same chromosomal region as the MDR-associated
genes MRP (ABCC1; 158343) and PRKCB1 (176970). The authors noted that
acute myeloid leukemia patients with a deletion of an MRP gene,
resulting from a chromosome 16 inversion, often have a favorable
outcome.
ANIMAL MODEL
Kowalski et al. (2007) found that Mvp -/- mice infected with P.
aeruginosa internalized fewer bacteria in lung epithelial cells than
wildtype mice, resulting in increased bacterial burden in the lung. Mvp
-/- mice also had increased mortality after P. aeruginosa infection.
Kowalski et al. (2007) concluded that MVP contributes to resistance
against P. aeruginosa lung infection.
*FIELD* RF
1. Abbondanza, C.; Rossi, V.; Roscigno, A.; Gallo, L.; Belsito, A.;
Piluso, G.; Medici, N.; Nigro, V.; Molinari, A. M.; Moncharmont, B.;
Puca, G. A.: Interaction of vault particles with estrogen receptor
in the MCF-7 breast cancer cell. J. Cell Biol. 141: 1301-1310, 1998.
2. Holzmann, K.; Ambrosch, I.; Elbling, L.; Micksche, M.; Berger,
W.: A small upstream open reading frame causes inhibition of human
major vault protein expression from a ubiquitous mRNA splice variant. FEBS
Lett. 494: 99-104, 2001.
3. Izquierdo, M. A.; Scheffer, G. L.; Flens, M. J.; Giaccone, G.;
Broxterman, H. J.; Meijer, C. J. L. M.; van der Valk, P.; Scheper,
R. J.: Broad distribution of the multidrug resistance-related vault
lung resistance protein in normal human tissues and tumors. Am. J.
Path. 148: 877-887, 1996.
4. Kickhoefer, V. A.; Rajavel, K. S.; Scheffer, G. L.; Dalton, W.
S.; Scheper, R. J.; Rome, L. H.: Vaults are up-regulated in multidrug-resistant
cancer cell lines. J. Biol. Chem. 273: 8971-8974, 1998.
5. Kickhoefer, V. A.; Siva, A. C.; Kedersha, N. L.; Inman, E. M.;
Ruland, C.; Streuli, M.; Rome, L. H.: The 193-kD vault protein, VPARP,
is a novel poly(ADP-ribose) polymerase. J. Cell Biol. 146: 917-928,
1999.
6. Kickhoefer, V. A.; Stephen, A. G.; Harrington, L.; Robinson, M.
O.; Rome, L. H.: Vaults and telomerase share a common subunit, TEP1. J.
Biol. Chem. 274: 32712-32717, 1999.
7. Kowalski, M. P.; Dubouix-Bourandy, A.; Bajmoczi, M.; Golan, D.
E.; Zaidi, T.; Coutinho-Sledge, Y. S.; Gygi, M. P.; Gygi, S. P.; Wiemer,
E. A. C.; Pier, G. B.: Host resistance to lung infection mediated
by major vault protein in epithelial cells. Science 317: 130-132,
2007.
8. Lange, C.; Walther, W.; Schwabe, H.; Stein, U.: Cloning and initial
analysis of the human multidrug resistance-related MVP/LRP gene promoter. Biochem.
Biophys. Res. Commun. 278: 125-133, 2000.
9. Scheffer, G. L.; Wijngaard, P. L. J.; Flens, M. J.; Izquierdo,
M. A.; Slovak, M. L.; Pinedo, H. M.; Meijer, C. J. L. M.; Clevers,
H. C.; Scheper, R. J.: The drug resistance-related protein LRP is
the human major vault protein. Nature Med. 1: 578-582, 1995.
10. Slesina, M.; Inman, E. M.; Rome, L. H.; Volknandt, W.: Nuclear
localization of the major vault protein in U373 cells. Cell Tissue
Res. 321: 97-104, 2005.
11. van Zon, A.; Mossink, M. H.; Schoester, M.; Scheffer, G. L.; Scheper,
R. J.; Sonneveld, P.; Wiemer, E. A. C.: Structural domains of vault
proteins: a role for the coiled coil domain in vault assembly. Biochem.
Biophys. Res. Commun. 291: 535-541, 2002.
12. Yu, Z.; Fotouhi-Ardakani, N.; Wu, L.; Maoui, M.; Wang, S.; Banville,
D.; Shen, S.-H.: PTEN associates with the vault particles in HeLa
cells. J. Biol. Chem. 277: 40247-40252, 2002.
*FIELD* CN
Patricia A. Hartz - updated: 3/6/2009
Paul J. Converse - updated: 7/17/2007
Patricia A. Hartz - updated: 7/30/2002
*FIELD* CD
Paul J. Converse: 6/28/2000
*FIELD* ED
mgross: 03/26/2009
terry: 3/6/2009
mgross: 7/18/2007
terry: 7/17/2007
carol: 7/30/2002
mgross: 8/11/2000
mgross: 6/29/2000
mgross: 6/28/2000