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227  structures 77  species 1  interaction 662  sequences 12  architectures

Family: Vault (PF01505)

Summary: Major Vault Protein repeat

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This is the Wikipedia entry entitled "Vault (organelle)". More...

Vault (organelle) Edit Wikipedia article

Major Vault Protein repeat
穹窿体.jpg
Structure of the Vault complex from rat liver.[1]
Identifiers
Symbol Vault
Pfam PF01505
InterPro IPR002499
PROSITE PDOC51224

The vault or vault cytoplasmic ribonucleoprotein is a eukaryotic organelle whose function is not fully understood. Discovered and successfully isolated by cell biologist Nancy Kedersha and biochemist Leonard Rome of the UCLA School of Medicine in the 1980s, vaults are cytoplasmic organelles which under an electron microscope resemble the arches of a cathedral vault, with 39-fold symmetry.[1] They are present in many types of eukaryotic cells and appear to be highly conserved amongst eukaryotes.[2] Vaults become part of lipid rafts where they may play a role fighting pathogens.[3]

Morphology[edit]

Vaults are large ribonucleoprotein particles. About 3 times the size of a ribosome and weighing approximately 13 MDa, they are found in many diverse eukaryotic cells. They measure 34 nm by 60 nm from a negative stain, 26 nm by 49 nm from cryo-electron microscopy, and 35 nm by 59 nm from STEM.[4] The vaults consist primarily of proteins, making it difficult to stain with conventional techniques. The protein structure consists of many major vault proteins (MVP) bound to one of the two minor vault proteins. Two large complexes of several MVP's and a minor vault protein close together to form the barrel-like vault organelle. They also contain small vault RNAs (vRNAs, also known as vtRNAs) of 86–141 bases within.[5]

Function[edit]

Despite not being fully elucidated, vaults have been associated with the nuclear pore complexes and their octagonal shape appears to support this.[6] It has been concluded that the vault's function is the transportation of molecules, such as mRNA, from the nucleus to parts of the cytoplasm.[7] It is also thought that vaults play a role in protein synthesis.[8]

Association with cancer[edit]

In the late 1990s, researchers found that vaults (especially the MVP) were over-expressed in cancer patients who were diagnosed with multidrug resistance, that is the resistance against many chemotherapy treatments.[9] Although this does not prove that increased number of vaults led to drug resistance, it does hint at some sort of involvement. This has potential in discovering the mechanisms behind drug-resistance in tumor cells and improving anticancer drugs.[10]

Evolutionary conservation[edit]

Vaults have been identified in mammals, amphibians, avians and Dictyostelium discoideum.[2] The Vault model used by the Pfam database identifies homologues in Paramecium tetraurelia, Kinetoplastida, many vertebrates, a cnidarian (starlet sea anemone), molluscs, Trichoplax adhaerens, flatworms, Echinococcus granulosus and Choanoflagellate.[11]

Although vaults have been observed in many eukaryotic species, a few species do not appear to have the protein. These include:[12]

These four species are model organisms for plants, nematodes, animal genetics and fungi respectively. Despite these exceptions, the high degree of similarity of vaults in organisms that do have them implies some sort of evolutionary importance.[2]

See also[edit]

External links[edit]

References[edit]

  1. ^ a b Tanaka H, Kato K, Yamashita E, et al. (January 2009). "The structure of rat liver vault at 3.5 angstrom resolution". Science 323 (5912): 384–8. doi:10.1126/science.1164975. PMID 19150846. 
  2. ^ a b c Kedersha NL, Miquel MC, Bittner D, Rome LH (1990). "Vaults. II. Ribonucleoprotein structures are highly conserved among higher and lower eukaryotes.". J Cell Biol 110 (4): 895–901. doi:10.1083/jcb.110.4.895. PMC 2116106. PMID 1691193. 
  3. ^ Tanaka H, Kato K, Yamashita E, et al. (January 2009). "The structure of rat liver vault at 3.5 angstrom resolution". Science 323 (5912): 384–8. doi:10.1126/science.1164975. PMID 19150846. 
  4. ^ Kedersha N. L., Heuser J. E., Chugani D. C., Rome L. H. (1991). "Vaults. III. Vault ribonucleoprotein particles open into flower-like structures with octagonal symmetry". J. Cell Biol 112 (2): 225–235. doi:10.1083/jcb.112.2.225. PMC 2288824. PMID 1988458. 
  5. ^ van Zon A, Mossink MH, Scheper RJ, Sonneveld P, Wiemer EA (September 2003). "The vault complex". Cell. Mol. Life Sci. 60 (9): 1828–37. doi:10.1007/s00018-003-3030-y. PMID 14523546. 
  6. ^ Unwin P. N. T., Milligan R. A. (1982). "A large particle associated with the perimeter of the nuclear pore complex". J. Cell Biol 93 (1): 63–75. doi:10.1083/jcb.93.1.63. PMC 2112107. PMID 7068761. 
  7. ^ Chugani DC, Rome LH, Kedersha NL (September 1993). "Evidence that vault ribonucleoprotein particles localize to the nuclear pore complex". J. Cell. Sci. 106: 23–9. PMID 8270627. 
  8. ^ Cannon, Joseph N.; Stanfield, Cindy L; Niles, Mary Jane; Germann, William J (2007). Principles of human physiology (3rd ed.). San Francisco: Pearson/Benjamin Cummings. p. 41. ISBN 978-0-8053-8286-0. 
  9. ^ Mossink MH, van Zon A, Scheper RJ, Sonneveld P, Wiemer EA (October 2003). "Vaults: a ribonucleoprotein particle involved in drug resistance?". Oncogene 22 (47): 7458–67. doi:10.1038/sj.onc.1206947. PMID 14576851. 
  10. ^ Kickhoefer VA, Vasu SK, Rome LH (May 1996). "Vaults are the answer, what is the question?". Trends Cell Biol. 6 (5): 174–8. doi:10.1016/0962-8924(96)10014-3. PMID 15157468. 
  11. ^ http://pfam.sanger.ac.uk/family/PF01505 Major Vault Protein repeat Pfam family
  12. ^ Rome L, Kedersha N, Chugani D (1991). "Unlocking vaults: organelles in search of a function.". Trends Cell Biol 1 (2-3): 47–50. doi:10.1016/0962-8924(91)90088-Q. PMID 14731565. 

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Major Vault Protein repeat Provide feedback

The vault is a ubiquitous and highly conserved ribonucleoprotein particle of approximately 13 mDa of unknown function [1]. This family corresponds to a repeat found in the amino terminal half of the major vault protein.

Literature references

  1. Kong LB, Siva AC, Rome LH, Stewart PL , Structure 1999;7:371-379.: Structure of the vault, a ubiquitous celular component. PUBMED:10196123 EPMC:10196123


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR002499

Vaults are the largest ribonucleoprotein particles known, having a mass of approximately 13 MDa. They are multi-subunit structures that may act as scaffolds for proteins involved in signal transduction and may also play a role in nucleo-cytoplasmic transport. Vaults are present in most normal tissues, but are more highly expressed 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 [PUBMED:16918321]. Overexpression of these proteins is linked with multidrug-resistance in cancer cells.

The mammalian vault structure is highly regular and consists of approximately 96 molecules of the 100 kDa major vault protein (MVP), 2 molecules of the 240 kDa minor vault protein TEP1, 8 molecules of the 193 kDa minor vault protein VPARP and at least 6 copies of a small untranslated RNA of 88-141 bases. The MVP molecules form the core of the complex, which is a barrel-like structure with an invaginated waist and two protruding caps. The complex can unfold into two symmetrical flower-like structures with 8 petals each supposedly consisting of 6 MVP molecules [PUBMED:10196123].

The MVP protein is composed of two distinct domains [PUBMED:16373071]. The N-terminal domain contains ~8 copies of the vault repeat (or MVP repeat) in tandem. The MVP repeat is composed of ~53 amino acids and forms a structural part of the vault wall. The C-terminal part of MVP may be involved in oligomerization and be located in the vault cap, while the MVP repeats in the N-terminal part can be packed like staves in a barrel to form the vault wall. The 3D structure of the repeat forms a fold that consists of a three stranded (B) antiparallel beta-sheet in a unique topology B2-B1-B3 and two loops. MVP repeats can be interaction-mediating modules, as MVP repeats 3 and 4 bind VPARP, which is one of the other vault proteins.

Domain organisation

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Alignments

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(85)
Full
(662)
Representative proteomes NCBI
(619)
Meta
(5)
RP15
(173)
RP35
(214)
RP55
(257)
RP75
(332)
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  Seed
(85)
Full
(662)
Representative proteomes NCBI
(619)
Meta
(5)
RP15
(173)
RP35
(214)
RP55
(257)
RP75
(332)
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  Seed
(85)
Full
(662)
Representative proteomes NCBI
(619)
Meta
(5)
RP15
(173)
RP35
(214)
RP55
(257)
RP75
(332)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

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This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Bateman A
Previous IDs: none
Type: Repeat
Author: Bateman A
Number in seed: 85
Number in full: 662
Average length of the domain: 43.50 aa
Average identity of full alignment: 31 %
Average coverage of the sequence by the domain: 23.60 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.0 8.3
Trusted cut-off 22.7 8.5
Noise cut-off 19.3 8.2
Model length: 43
Family (HMM) version: 13
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Species distribution

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Interactions

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Vault

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Vault domain has been found. There are 227 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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