Reviewed, UniProtKB/Swiss-Prot Q14764 (MVP_HUMAN)

Names and origin

Protein names

Recommended name:
    Major vault protein
      Short name=MVP
Alternative name(s):
    Lung resistance-related protein

Gene names

Name:	MVP
Synonyms:	LRP

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	893 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Required for normal vault structure. Vaults are multi-subunit structures that may act as scaffolds for proteins involved in signal transduction. Vaults may also play a role in nucleo-cytoplasmic transport. Down-regulates INFG-mediated STAT1 signaling and subsequent activation of JAK. Down-regulates SRC activity and signaling through MAP kinases. Ref.9 Ref.11 Ref.12
Subunit structure	The vault ribonucleoprotein particle is a huge (400 A x 670 A) cage structure of 12.9 Mda, it consists of a dimer of half-vaults, with each half-vault comprising 39 identical major vault protein (MVP) chains, PARP4 and one or more vault RNAs (vRNAs). Interacts with TEP1. Interacts with PTEN and activated MAPK1. The phosphorylated protein interacts with the SH2 domains of PTPN11 and SRC. Ref.9 Ref.11 Ref.8 Ref.14
Subcellular location	Cytoplasm. Nucleus › nuclear pore complex. Note: 5% found in the nuclear pore complex. Translocates from the nucleus to the cytoplasm upon EGF treatment. Ref.9 Ref.11
Tissue specificity	Present in most normal tissues. Higher expression observed in epithelial cells with secretory and excretory functions, as well as in cells chronically exposed to xenobiotics, such as bronchial cells and cells lining the intestine. Overexpressed in many multidrug-resistant cancer cells.
Induction	Up-regulated by IFNG. Ref.12
Domain	MVP 3 mediates interaction with PTEN. MVP 4 mediates interaction with PARP4.
Post-translational modification	Phosphorylated on Tyr residues after EGF stimulation. Ref.9 Ref.11 Ref.10 Ref.13 Dephosphorylated by PTPN11. Ref.9 Ref.11 Ref.10 Ref.13
Sequence similarities	Contains 9 MVP (vault) repeats.

Ontologies

Keywords
Biological process	Protein transport Translocation Transport mRNA transport
Cellular component	Cytoplasm Nuclear pore complex Nucleus
Coding sequence diversity	Polymorphism
Domain	Repeat
Molecular function	Ribonucleoprotein
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	mRNA transport Inferred from electronic annotation. Source: UniProtKB-KW protein transport Inferred from electronic annotation. Source: UniProtKB-KW response to drug Ref.1 Traceable author statement. Source: ProtInc transmembrane transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Ref.1 Inferred from direct assay. Source: HPA nuclear pore Inferred from electronic annotation. Source: UniProtKB-SubCell ribonucleoprotein complex Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.6

Chain

2 – 893

892

Major vault protein

PRO_0000158980

Regions

Repeat

2 – 56

55

MVP 1

Repeat

57 – 111

55

MVP 2

Repeat

112 – 164

53

MVP 3

Repeat

165 – 217

53

MVP 4

Repeat

218 – 272

55

MVP 5

Repeat

273 – 323

51

MVP 6

Repeat

324 – 379

56

MVP 7

Repeat

380 – 457

78

MVP 8

Repeat

458 – 520

63

MVP 9

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.6

Modified residue

13

1

Phosphotyrosine Ref.9 Ref.10

Modified residue

15

1

Phosphotyrosine Ref.9 Ref.13

Natural variations

Natural variant

635

1

V → I: dbSNP rs35916172.

VAR_050179

Natural variant

651

1

R → Q: dbSNP rs3764944.

VAR_050180

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

893

Helix Strand Turn

Details...

Beta strand

120 – 125

6

Beta strand

137 – 139

3

Beta strand

141 – 147

7

Helix

148 – 150

3

Beta strand

157 – 163

7

Beta strand

170 – 181

12

Beta strand

185 – 187

3

Beta strand

195 – 198

4

Beta strand

208 – 217

10

Sequences

	Sequence		Length	Mass (Da)
	Q14764-1 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: 6FEE5545B0A3FE65	FASTA	893	99,327
	10 20 30 40 50 60 MATEEFIIRI PPYHYIHVLD QNSNVSRVEV GPKTYIRQDN ERVLFAPMRM VTVPPRHYCT 70 80 90 100 110 120 VANPVSRDAQ GLVLFDVTGQ VRLRHADLEI RLAQDPFPLY PGEVLEKDIT PLQVVLPNTA 130 140 150 160 170 180 LHLKALLDFE DKDGDKVVAG DEWLFEGPGT YIPRKEVEVV EIIQATIIRQ NQALRLRARK 190 200 210 220 230 240 ECWDRDGKER VTGEEWLVTT VGAYLPAVFE EVLDLVDAVI LTEKTALHLR ARRNFRDFRG 250 260 270 280 290 300 VSRRTGEEWL VTVQDTEAHV PDVHEEVLGV VPITTLGPHN YCVILDPVGP DGKNQLGQKR 310 320 330 340 350 360 VVKGEKSFFL QPGEQLEQGI QDVYVLSEQQ GLLLRALQPL EEGEDEEKVS HQAGDHWLIR 370 380 390 400 410 420 GPLEYVPSAK VEVVEERQAI PLDENEGIYV QDVKTGKVRA VIGSTYMLTQ DEVLWEKELP 430 440 450 460 470 480 PGVEELLNKG QDPLADRGEK DTAKSLQPLA PRNKTRVVSY RVPHNAAVQV YDYREKRARV 490 500 510 520 530 540 VFGPELVSLG PEEQFTVLSL SAGRPKRPHA RRALCLLLGP DFFTDVITIE TADHARLQLQ 550 560 570 580 590 600 LAYNWHFEVN DRKDPQETAK LFSVPDFVGD ACKAIASRVR GAVASVTFDD FHKNSARIIR 610 620 630 640 650 660 TAVFGFETSE AKGPDGMALP RPRDQAVFPQ NGLVVSSVDV QSVEPVDQRT RDALQRSVQL 670 680 690 700 710 720 AIEITTNSQE AAAKHEAQRL EQEARGRLER QKILDQSEAE KARKELLELE ALSMAVESTG 730 740 750 760 770 780 TAKAEAESRA EAARIEGEGS VLQAKLKAQA LAIETEAELQ RVQKVRELEL VYARAQLELE 790 800 810 820 830 840 VSKAQQLAEV EVKKFKQMTE AIGPSTIRDL AVAGPEMQVK LLQSLGLKST LITDGSTPIN 850 860 870 880 890 LFNTAFGLLG MGPEGQPLGR RVASGPSPGE GISPQSAQAP QAPGDNHVVP VLR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The drug resistance-related protein LRP is the human major vault protein." 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. Nat. Med. 1:578-582(1995) [PubMed: 7585126] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	Scheffer G.L. Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO C-TERMINUS.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Eye.
[4]	"Cloning and initial analysis of the human multidrug resistance-related MVP/LRP gene promoter." Lange C., Walther W., Schwabe H., Stein U. Biochem. Biophys. Res. Commun. 278:125-133(2000) [PubMed: 11071864] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-169.
[5]	"A small upstream open reading frame causes inhibition of human major vault protein expression from a ubiquitous mRNA splice variant." Holzmann K., Ambrosch I., Elbling L., Micksche M., Berger W. FEBS Lett. 494:99-104(2001) [PubMed: 11297743] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 1-65. Tissue: Lung cancer.
[6]	Quadroni M., Potts A., Barblan J., Bienvenut W.V. Submitted (JAN-2005) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-9; 68-82 AND 462-474, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, MASS SPECTROMETRY. Tissue: Melanoma.
[7]	"Vaults and telomerase share a common subunit, TEP1." Kickhoefer V.A., Stephen A.G., Harrington L., Robinson M.O., Rome L.H. J. Biol. Chem. 274:32712-32717(1999) [PubMed: 10551828] [Abstract] Cited for: ASSOCIATION WITH TEP1.
[8]	"PTEN associates with the vault particles in HeLa cells." Yu Z., Fotouhi-Ardakani N., Wu L., Maoui M., Wang S., Banville D., Shen S.-H. J. Biol. Chem. 277:40247-40252(2002) [PubMed: 12177006] [Abstract] Cited for: INTERACTION WITH PTEN.
[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.C., Bennett A.M. J. Biol. Chem. 279:29374-29385(2004) [PubMed: 15133037] [Abstract] Cited for: PHOSPHORYLATION AT TYROSINE RESIDUES, MASS SPECTROMETRY, INTERACTION WITH PTPN11, SUBCELLULAR LOCATION, FUNCTION.
[10]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-13, MASS SPECTROMETRY.
[11]	"Crosstalk between Src and major vault protein in epidermal growth factor-dependent cell signalling." Kim E., Lee S., Mian M.F., Yun S.U., Song M., Yi K.-S., Ryu S.H., Suh P.-G. FEBS J. 273:793-804(2006) [PubMed: 16441665] [Abstract] Cited for: FUNCTION, INTERACTION WITH SRC, TYROSINE PHOSPHORYLATION, SUBCELLULAR LOCATION, MASS SPECTROMETRY.
[12]	"The major vault protein is responsive to and interferes with interferon-gamma-mediated STAT1 signals." Steiner E., Holzmann K., Pirker C., Elbling L., Micksche M., Sutterluety H., Berger W. J. Cell Sci. 119:459-469(2006) [PubMed: 16418217] [Abstract] Cited for: INDUCTION, FUNCTION.
[13]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-15, MASS SPECTROMETRY.
[14]	"Solution structure of a two-repeat fragment of major vault protein." Kozlov G., Vavelyuk O., Minailiuc O., Banville D., Gehring K., Ekiel I. J. Mol. Biol. 356:444-452(2006) [PubMed: 16373071] [Abstract] Cited for: STRUCTURE BY NMR OF 113-221, INTERACTION WITH PARP4.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBLGenBankDDBJ

X79882 mRNA. Translation: CAA56256.2.
BC015623 mRNA. Translation: AAH15623.1.
AJ238512 , AJ238514, AJ238516, AJ238518 Genomic DNA. Translation: CAB55354.1.
AJ238519 , AJ238514, AJ238516, AJ238518 Genomic DNA. Translation: CAB55355.1.
AJ291365 Genomic DNA. Translation: CAC35313.1.
AJ291366 mRNA. Translation: CAC35314.1.
AJ291367 mRNA. Translation: CAC35316.1.

IPI

IPI00000105.

PIR

S57723.

RefSeq

NP_005106.2.
NP_059447.2.

UniGene

Hs.632177

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1Y7X	NMR	-	A	113-221	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

Q14764.

PTM databases

PhosphoSite

Q14764.

2-D gel databases

OGP

Q14764.

REPRODUCTION-2DPAGE

IPI00000105.

Proteomic databases

PeptideAtlas

Q14764.

PRIDE

Q14764.

Genome annotation databases

Ensembl

ENST00000357402; ENSP00000349977; ENSG00000013364; Homo sapiens. [Genome view]
ENST00000395353; ENSP00000378760; ENSG00000013364; Homo sapiens. [Genome view]
ENST00000424666; ENSP00000387497; ENSG00000013364; Homo sapiens. [Genome view]
ENST00000452209; ENSP00000387916; ENSG00000013364; Homo sapiens. [Genome view]

GeneID

9961.

KEGG

hsa:9961.

UCSC

uc002dui.1. human.

Organism-specific databases

CTD

9961.

GeneCards

GC16P029739.

H-InvDB

HIX0012947.

HGNC

HGNC:7531. MVP.

HPA

CAB002752.
CAB022717.
HPA002321.

MIM

605088. gene.

PharmGKB

PA31332.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q14764.

HOVERGEN

Q14764.

OMA

SYRVPHN.

Gene expression databases

ArrayExpress

Q14764.

Bgee

Q14764.

CleanEx

HS_MVP.

Genevestigator

Q14764.

GermOnline

ENSG00000013364. Homo sapiens.

Family and domain databases

InterPro

IPR002499. Vault_N.
[Graphical view]

Pfam

PF01505. Vault. 7 hits.
[Graphical view]

PROSITE

PS51224. MVP. 8 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

37586.

SOURCE

Search...

Entry information

Entry name

MVP_HUMAN

Accession

Primary (citable) accession number: Q14764
Secondary accession number(s): Q96BG4 , Q9BPW6, Q9BQT1, Q9UBD1

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	January 23, 2007
Last modified:	November 3, 2009
This is version 89 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.