A0A059PCL4 · A0A059PCL4_9REOV

Function

function

Outer capsid protein VP4: Spike-forming protein that mediates virion attachment to the host epithelial cell receptors and plays a major role in cell penetration, determination of host range restriction and virulence. Rotavirus attachment and entry into the host cell probably involves multiple sequential contacts between the outer capsid proteins VP4 and VP7, and the cell receptors. It is subsequently lost, together with VP7, following virus entry into the host cell. Following entry into the host cell, low intracellular or intravesicular Ca2+ concentration probably causes the calcium-stabilized VP7 trimers to dissociate from the virion. This step is probably necessary for the membrane-disrupting entry step and the release of VP4, which is locked onto the virion by VP7. During the virus exit from the host cell, VP4 seems to be required to target the newly formed virions to the host cell lipid rafts.
Outer capsid protein VP5*: Forms the spike 'foot' and 'body' and acts as a membrane permeabilization protein that mediates release of viral particles from endosomal compartments into the cytoplasm. During entry, the part of VP5* that protrudes from the virus folds back on itself and reorganizes from a local dimer to a trimer. This reorganization may be linked to membrane penetration by exposing VP5* hydrophobic region. In integrin-dependent strains, VP5* targets the integrin heterodimer ITGA2/ITGB1 for cell attachment.
Outer capsid protein VP8*: Forms the head of the spikes and mediates the recognition of specific host cell surface glycans. It is the viral hemagglutinin and an important target of neutralizing antibodies. In sialic acid-dependent strains, VP8* binds to host cell sialic acid, most probably a ganglioside, providing the initial contact. In some other strains, VP8* mediates the attachment to histo-blood group antigens (HBGAs) for viral entry.

Miscellaneous

In group A rotaviruses, VP4 defines the P serotype.
Some rotavirus strains are neuraminidase-sensitive and require sialic acid to attach to the cell surface. Some rotavirus strains are integrin-dependent. Some rotavirus strains depend on ganglioside for their entry into the host cell. Hsp70 also seems to be involved in the entry of some strains.

Caution

Lacks conserved residue(s) required for the propagation of feature annotation.

Features

Showing features for site.

TypeIDPosition(s)Description
Site231-232Cleavage
Site241-242Cleavage
Site247-248Cleavage; associated with enhancement of infectivity

GO annotations

AspectTerm
Cellular Componenthost cell endoplasmic reticulum-Golgi intermediate compartment
Cellular Componenthost cell plasma membrane
Cellular Componenthost cell rough endoplasmic reticulum
Cellular Componenthost cytoskeleton
Cellular Componentmembrane
Cellular Componentviral outer capsid
Biological Processpermeabilization of host organelle membrane involved in viral entry into host cell
Biological Processvirion attachment to host cell

Keywords

Names & Taxonomy

Protein names

Gene names

    • Name
      VP4

Organism names

  • Taxonomic identifier
  • Strain
    • RVA/Pig-wt/ITA/2CR/2009/G9P[23]
  • Taxonomic lineage
    Viruses > Riboviria > Orthornavirae > Duplornaviricota > Resentoviricetes > Reovirales > Sedoreoviridae > Rotavirus > Rotavirus A

Accessions

  • Primary accession
    A0A059PCL4

Proteomes

Subcellular Location

Virion

Outer capsid protein VP5*

Virion
Note: Outer capsid protein.

Outer capsid protein VP8*

Virion
Note: Outer capsid protein.

Outer capsid protein VP4

Virion
Host cell membrane
Note: The outer layer contains 180 copies of VP4, grouped as 60 dimers. Immature double-layered particles assembled in the cytoplasm bud across the membrane of the endoplasmic reticulum, acquiring during this process a transient lipid membrane that is modified with the ER resident viral glycoproteins NSP4 and VP7; these enveloped particles also contain VP4. As the particles move towards the interior of the ER cisternae, the transient lipid membrane and the non-structural protein NSP4 are lost, while the virus surface proteins VP4 and VP7 rearrange to form the outermost virus protein layer, yielding mature infectious triple-layered particles. VP4 also seems to associate with lipid rafts of the host cell membrane probably for the exit of the virus from the infected cell by an alternate pathway.

Keywords

PTM/Processing

Features

Showing features for chain, disulfide bond.

TypeIDPosition(s)Description
ChainPRO_50290669881-231Outer capsid protein VP8*
ChainPRO_50233735911-776Outer capsid protein VP4
Disulfide bond203↔216
ChainPRO_5029066989248-776Outer capsid protein VP5*
Disulfide bond318↔380

Post-translational modification

Outer capsid protein VP4: Proteolytic cleavage by trypsin results in activation of VP4 functions and greatly increases infectivity. The penetration into the host cell is dependent on trypsin treatment of VP4. It produces two peptides, VP5* and VP8* that remain associated with the virion. Cleavage of VP4 by trypsin probably occurs in vivo in the lumen of the intestine prior to infection of enterocytes. Trypsin seems to be incorporated into the three-layered viral particles but remains inactive as long as the viral outer capsid is intact and would only be activated upon the solubilization of the latter.

Keywords

Interaction

Subunit

Outer capsid protein VP4: Homotrimer. VP4 adopts a dimeric appearance above the capsid surface, while forming a trimeric base anchored inside the capsid layer. Only hints of the third molecule are observed above the capsid surface. It probably performs a series of molecular rearrangements during viral entry. Prior to trypsin cleavage, it is flexible. The priming trypsin cleavage triggers its rearrangement into rigid spikes with approximate two-fold symmetry of their protruding parts. After an unknown second triggering event, cleaved VP4 may undergo another rearrangement, in which two VP5* subunits fold back on themselves and join a third subunit to form a tightly associated trimer, shaped like a folded umbrella. Outer capsid protein VP4: Interacts with VP6. Outer capsid protein VP4: Interacts with VP7. Outer capsid protein VP5*: Homotrimer. The trimer is coiled-coil stabilized by its C-terminus, however, its N-terminus, known as antigen domain or 'body', seems to be flexible allowing it to self-associate either as a dimer or a trimer.

Family & Domains

Features

Showing features for domain, region, motif, coiled coil.

TypeIDPosition(s)Description
Domain65-224Haemagglutinin outer capsid protein VP4 concanavalin-like
Region65-224Spike head
Region248-479Spike body and stalk (antigen domain)
Domain250-474Rotavirus VP4 membrane interaction
Motif308-310DGE motif; interaction with ITGA2/ITGB1 heterodimer
Region389-409Hydrophobic; possible role in virus entry into host cell
Motif448-450YGL motif; interaction with ITGA4
Coiled coil484-518
Domain486-776Rotavirus VP4 helical
Region510-776Spike foot
Motif644-646KID motif; interaction with HSPA8

Domain

Outer capsid protein VP4: The VP4 spike is divided into a foot, a stalk and body, and a head.

Sequence similarities

Belongs to the rotavirus VP4 family.

Keywords

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    776
  • Mass (Da)
    86,684
  • Last updated
    2014-09-03 v1
  • Checksum
    2B59894BDAE5542D
MASLIYRQLLSNSYTVDLSDEIQTIGSEKTQNVTINPGPFAQTGYAPVNWGPGETNDSTTIEPVLDGPYQPTSFNPPVSYWILLSPSSAGVVVEGTNNSDRWLATILIEPNVTSQSRTYILFGQQEQITIENTSMTKWKFVDLAKTDVNGTFTQHGPLLSDTKLYGVMKFSGKLYTYNGETPNATTGYYTTTNYDTVTMISHCDFYIIPRSEENACTNYINNGLPPIQNTRNVVPVSLTSRSIVYTRAQANEDIIVSKTSLWKEMQYNRDITIRFKFANAIIKSGGLGYKWSEISFKPANYQYNYTRDGELITAHTTCSVNGINDFSYNGGSLPTDFVISRYEVIKENSYVYVDYWDDSQAFRNMVYVRSLAANLNSVICTGGNYDFRLPVGAWPVMTGGAVSLRPAGVTLSTQFTDFVSLNSLRFRFSLSVEEPPFAIARTRVSSLYGLPAANPNNGKDYYEILGRFSLISLVPSNDDYQTPIMNSVTVRQDLERQLNELRQEFNSLSQEIAMSQLIDLALLPLDMFSMFTGIKSTIDAAKSMATNVMKRFKRSNLASSISTLTDSLSDAASSISRNSSIRSVGSSVSAWTDISTQLTDVSDALNSVSTQTSAISRRLRLKEITTQTEGMNFDDISAAVLKTKIDKSTQISSTTLPDVVTEASEKFIPNRAYRVIKDDEVLEAGTDGRFFAYKVDTFDEIPFDVQKFADLITDSPVISAIIDFKTLKNLNDNYGITREQAFNLLRSDPRVLREFINQDNPIIRNRIEQLILQCRL

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
KC610681
EMBL· GenBank· DDBJ
AGI43653.1
EMBL· GenBank· DDBJ
Genomic RNA

Similar Proteins

Disclaimer

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