{PDOC52083}
{PS52083; MVP_SHOULDER}
{BEGIN}
*****************************************************
* Major vault protein (MVP) shoulder domain profile *
*****************************************************

The vault   is   the  biggest  ribonucleoprotein  organelle  present  in  many
eukaryotic cells,  three  times  the  size  of  a  ribosome.  Vaults have been
identified in  a  wide  variety  of  species,  including mammals, birds, fish,
echinoids and  slime  molds. Although several functions have been proposed for
vaults since their discovery in 1986, including roles in multidrug resistance,
cell signaling,  and innate immunity, their cellular function remains unclear.
Most vault  particles are present in the cytoplasm, but a few of them localize
to the  nucleus.  Mammalian  vaults are composed of major vault protein (MVP),
telomerase-associated protein  1  (TEP1),  vault  poly(ADP-ribose)  polymerase
(VPARP) and vault RNA vRNA. MVP is the main constituent of the vault organelle
and is sufficient to give the vault its hollow barrel-like shape [1,2,3,4].

Each MVP  monomer  folds  into 12 domains: nine structural repeat domains (see
<PDOC51224>), a  shoulder  domain,  a  cap-helix  domain and a cap-ring domain
[1,2].

The MVP  shoulder domain folds into a single alpha/beta globular domain with a
four-stranded antiparallel  beta  sheet  on one side and four alpha helices on
the other  side  (see <PDB:2QZV>). The shoulder domain is structurally similar
to the  core  domain  of stomatin from Pyrococcus horikoshii (PhStoCD) and the
flotillin-2 band-7   domain   (FlotBD7).   The  core  domain  of  stomatin  is
evolutionarily conserved  and  falls within the stomatin-prohibitin-flotillin-
HflK-C (SPFH)  domain family. The SPFH domain is known to be involved in lipid
raft association.  The structural similarities between the shoulder domain and
SPFH domain  family  supports  an  interaction between MVP and lipid rafts-for
example, when  human  lung  epithelial  cells  are  infected  with Pseudomonas
aeruginosa [1,2,4].

The profile we developed covers the entire MVP shoulder domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: November 2025 / First entry.

[ 1] Tanaka H., Kato K., Yamashita E., Sumizawa T., Zhou Y., Yao M.,
     Iwasaki K., Yoshimura M., Tsukihara T.
     "The structure of rat liver vault at 3.5 angstrom resolution."
     Science 323:384-388(2009).
     PubMed=19150846; DOI=10.1126/science.1164975
[ 2] Tanaka H., Tsukihara T.
     "Structural studies of large nucleoprotein particles, vaults."
     Proc. Jpn. Acad. Ser. B. Phys. Biol. Sci. 88:416-433(2012).
     PubMed=23060231; DOI=10.2183/pjab.88.416
[ 3] Kretz P.F., Wagner C., Mikhaleva A., Montillot C., Hugel S.,
     Morella I., Kannan M., Fischer M.-C., Milhau M., Yalcin I.,
     Brambilla R., Selloum M., Herault Y., Reymond A., Collins S.C.,
     Yalcin B.
     "Dissecting the autism-associated 16p11.2 locus identifies multiple
     drivers in  neuroanatomical phenotypes and unveils a male-specific
     role for the major vault  protein."
     Genome Biol 24:261-261(2023).
     PubMed=37968726; DOI=10.1186/s13059-023-03092-8
[ 4] Loevestam S., Scheres S.H.W.
     "Cryo-EM structure of the vault from human brain reveals symmetry
     mismatch at its  caps."
     Structure 33:1643-1648.e1(2025).
     PubMed=40803316; DOI=10.1016/j.str.2025.07.014

--------------------------------------------------------------------------------
PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and
distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives
(CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html
--------------------------------------------------------------------------------

{END}