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HAMAP rule MF_04132

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General rule information [?]

Accession MF_04132
Dates 28-MAR-2018 (Created)
26-AUG-2021 (Last updated, Version 9)
Name Rota_A_VP4
Scope(s) Viruses
Rotavirus
Template(s) P12473 (VP4_ROTRH); Q96802 (VP4_ROTRF); A2T3T2 (VP4_ROTSH); P11193 (VP4_ROTHW); Q04916 (VP4_ROTGA); [ Recover all ]
Triggered by HAMAP; MF_04132 (Get profile general information and statistics)

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 [?]

FUNCTIONOuter 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 LOCATIONOuter 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.
DOMAINOuter capsid protein VP4: The VP4 spike is divided into a foot, a stalk and body, and a head.
PTMOuter 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.
MISCELLANEOUSIn group A rotaviruses, VP4 defines the P serotype.
MISCELLANEOUSSome 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.
SIMILARITYBelongs to the rotavirus VP4 family.
case <FTTag:cleavage1> and (<FTTag:cleavage2> or <FTTag:cleavage3>)
FUNCTIONOuter 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.
FUNCTIONOuter 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.
SUBUNITOuter 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 LOCATIONOuter capsid protein VP8*: Virion. Note=Outer capsid protein.
SUBCELLULAR LOCATIONOuter capsid protein VP5*: Virion. Note=Outer capsid protein.
else case (<FTTag:cleavage2> or <FTTag:cleavage3>) and not <FTTag:cleavage1>
FUNCTIONOuter 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.
SUBUNITOuter 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 LOCATIONOuter capsid protein VP5*: Virion. Note=Outer capsid protein.
else case <FTTag:cleavage1> and not (<FTTag:cleavage2> or <FTTag:cleavage3>)
FUNCTIONOuter 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.
SUBUNITOuter 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 LOCATIONOuter capsid protein VP8*: Virion. Note=Outer capsid protein.
end case
case <FTGroup:1>
MISCELLANEOUSThis strain probably uses sialic acid to attach to the host cell.
end case

Keywords [?]

Capsid protein
case <FTTag:disulf>
Disulfide bond
end case
Hemagglutinin
Host cell membrane
Host cytoplasm
Host cytoskeleton
Host endoplasmic reticulum
Host membrane
Host-virus interaction
Membrane
Outer capsid protein
Viral attachment to host cell
Viral penetration into host cytoplasm
Viral penetration via permeabilization of host membrane
Virion
Virus entry into host cell

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;
Pfam PF00426; VP4_haemagglut; 1;
Pfam PF17478; VP4_helical; 1;
General Coiled_coil; -; 0-unlimited;

Features [?]

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

Additional information [?]

Size range 770-780 amino acids
Related rules MF_04125
Fusion Nter: None Cter: None



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