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Annotation rule MF_04132
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General rule information [?]

Accession MF_04132
Dates 28-MAR-2018 (Created)
6-FEB-2020 (Last updated, Version 8)
Name Rota_A_VP4
Scope
Viruses; Rotavirus
Templates P12473 (VP4_ROTRH); Q96802 (VP4_ROTRF); A2T3T2 (VP4_ROTSH); P11193 (VP4_ROTHW); Q04916 (VP4_ROTGA): [Recover all]

Propagated annotation [?]


Identifier, protein and gene names [?]

Identifier
VP4
case <FTTag:cleavage1> and (<FTTag:cleavage2> or <FTTag:cleavage3>)
Protein name
RecName: Full=Outer capsid protein VP4;
AltName: Full=Hemagglutinin;
Contains:
RecName: Full=Outer capsid protein VP8*;
Contains:
RecName: Full=Outer capsid protein VP5*;
else case <FTTag:cleavage1> and not (<FTTag:cleavage2> or <FTTag:cleavage3>)
Protein name
RecName: Full=Outer capsid protein VP4;
AltName: Full=Hemagglutinin;
Contains:
RecName: Full=Outer capsid protein VP8*;
else case (<FTTag:cleavage2> or <FTTag:cleavage3>) and not <FTTag:cleavage1>
Protein name
RecName: Full=Outer capsid protein VP4;
AltName: Full=Hemagglutinin;
Contains:
RecName: Full=Outer capsid protein VP5*;
else
Protein name
RecName: Full=Outer capsid protein VP4;
AltName: Full=Hemagglutinin;
end case

Comments [?]

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 Ca(2+) 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.
Subcellular location Outer capsid protein VP4: Virion. Host rough endoplasmic reticulum. Host cell membrane. Host cytoplasm, host cytoskeleton. Host endoplasmic reticulum-Golgi intermediate compartment. 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.
Domain Outer capsid protein VP4: The VP4 spike is divided into a foot, a stalk and body, and a head.
Ptm 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.
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.
Similarity Belongs to the rotavirus VP4 family.
case <FTTag:cleavage1> and (<FTTag:cleavage2> or <FTTag:cleavage3>)
Function 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.
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.
Subcellular location Outer capsid protein VP8*: Virion. Note=Outer capsid protein.
Outer capsid protein VP5*: Virion. Note=Outer capsid protein.
else case (<FTTag:cleavage2> or <FTTag:cleavage3>) and not <FTTag:cleavage1>
Function 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.
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.
Subcellular location Outer capsid protein VP5*: Virion. Note=Outer capsid protein.
else case <FTTag:cleavage1> and not (<FTTag:cleavage2> or <FTTag:cleavage3>)
Function 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.
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. Outer capsid protein VP4: Interacts with VP6. Outer capsid protein VP4: Interacts with VP7.
Subcellular location Outer capsid protein VP8*: Virion. Note=Outer capsid protein.
end case
case <FTGroup:1>
Miscellaneous This strain probably uses sialic acid to attach to the host cell.
end case

Keywords [?]

case <FTTag:disulf>
end case

Gene Ontology [?]

GO:0044168; Cellular component: host cell rough endoplasmic reticulum.
GO:0039624; Cellular component: viral outer capsid.
GO:0039665; Biological process: permeabilization of host organelle membrane involved in viral entry into host cell.
GO:0019062; Biological process: virion attachment to host cell.

Cross-references [?]

Pfam PF17477; Rota_VP4_MID; 1;
PF00426; VP4_haemagglut; 1;
PF17478; VP4_helical; 1;

Computed features [?]

General Coiled_coil; -; 0-unlimited; trigger=yes;

Features [?]

From: VP4_ROTRH (P12473)
Key     From     To       Description   Tag   Condition   FTGroup
CHAIN     Nter     Cter       Outer capsid protein VP4        
SITE (Optional)     231     232       Cleavage   cleavage1   [RT]-[NY]  
SITE     241     242       Cleavage     R-[NASTDEQ]  
SITE (Optional)     247     248       Cleavage; associated with enhancement of infectivity   cleavage2   [KR]-[AV]  
case <FTTag:cleavage1>
CHAIN     Nter     231       Outer capsid protein VP8*        
end case
case <FTTag:cleavage2>
CHAIN     248     Cter       Outer capsid protein VP5*        
end case
MOTIF     308     310       DGE motif; interaction with ITGA2/ITGB1 heterodimer     D-G-E  
MOTIF     448     450       YGL motif; interaction with ITGA4     Y-G-L  
MOTIF     644     646       KID motif; interaction with HSPA8     K-I-D  
REGION     51     78       Disorded; interaction with the intermediate capsid protein VP6        
REGION     312     326       Disorded        
REGION     389     409       Hydrophobic; possible role in virus entry into host cell        
REGION     65     224       Spike head        
REGION     248     479       Spike body and stalk (antigen domain)        
REGION     389     409       Hydrophobic; possible role in virus entry into host cell        
REGION     510     776       Spike foot        
SITE     101     101       Binding to sialic acid     R   1
SITE     190     190       Binding to sialic acid     S   1
DISULFID (Optional)     203     216           disulf   C-x*-C  
DISULFID (Optional)     318     380           disulf   C-x*-C  
From: VP4_ROTBU (P12474)
SITE (Optional)     246     247       Probable cleavage   cleavage3   [R]-[EIV]  
case <FTTag:cleavage3>
CHAIN     247     Cter       Outer capsid protein VP5*        
end case

Additional information [?]

Size range 770-780 amino acids
Related rules MF_04125 (VP4)
Fusion None