HAMAP rule MF_04125

General rule information [?]

Accession	MF_04125
Dates	28-MAR-2018 (Created) 6-FEB-2020 (Last updated, Version 6)
Name	Rota_VP4
Scope(s)	Viruses Rotavirus
Template(s)	Q82040 (VP4_ROTHC); P12473 (VP4_ROTRH); Q96802 (VP4_ROTRF); A2T3T2 (VP4_ROTSH); P11193 (VP4_ROTHW); [ Recover all ]
Triggered by	HAMAP; MF_04125 (Get profile general information and statistics)

Propagated annotation [?]

Identifier, protein and gene names [?]

Identifier	VP4
case <FTTag:cleavage1> and <FTTag:cleavage2>
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>
Protein name	RecName: Full=Outer capsid protein VP4; AltName: Full=Hemagglutinin; Contains: RecName: Full=Outer capsid protein VP8*;
else case <FTTag:cleavage2> 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.
SUBCELLULAR LOCATION	Outer capsid protein VP4: Virion. Host rough endoplasmic reticulum. Host cell membrane. 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.
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.
SIMILARITY	Belongs to the rotavirus VP4 family.
case <FTTag:cleavage1> and <FTTag:cleavage2>
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.
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.
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.
SUBCELLULAR LOCATION	Outer capsid protein VP5*: Virion. Note=Outer capsid protein.
else case <FTTag:cleavage2> 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.
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>
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.
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