AC   MF_04132;
DC   Protein; auto
TR   HAMAP; MF_04132; -; 1; level=0
XX
Names: Rota_A_VP4
XX
ID   VP4
case <FTTag:cleavage1> and (<FTTag:cleavage2> or <FTTag:cleavage3>)
DE   RecName: Full=Outer capsid protein VP4;
DE   AltName: Full=Hemagglutinin;
DE   Contains:
DE     RecName: Full=Outer capsid protein VP8*;
DE   Contains:
DE     RecName: Full=Outer capsid protein VP5*;
else case <FTTag:cleavage1> and not (<FTTag:cleavage2> or <FTTag:cleavage3>)
DE   RecName: Full=Outer capsid protein VP4;
DE   AltName: Full=Hemagglutinin;
DE   Contains:
DE     RecName: Full=Outer capsid protein VP8*;
else case (<FTTag:cleavage2> or <FTTag:cleavage3>) and not <FTTag:cleavage1>
DE   RecName: Full=Outer capsid protein VP4;
DE   AltName: Full=Hemagglutinin;
DE   Contains:
DE     RecName: Full=Outer capsid protein VP5*;
else
DE   RecName: Full=Outer capsid protein VP4;
DE   AltName: Full=Hemagglutinin;
end case
XX
CC   -!- FUNCTION: Outer capsid protein VP4: Spike-forming protein that mediates
CC       virion attachment to the host epithelial cell receptors and plays a
CC       major role in cell penetration, determination of host range restriction
CC       and virulence. Rotavirus attachment and entry into the host cell
CC       probably involves multiple sequential contacts between the outer capsid
CC       proteins VP4 and VP7, and the cell receptors. It is subsequently lost,
CC       together with VP7, following virus entry into the host cell. Following
CC       entry into the host cell, low intracellular or intravesicular Ca(2+)
CC       concentration probably causes the calcium-stabilized VP7 trimers to
CC       dissociate from the virion. This step is probably necessary for the
CC       membrane-disrupting entry step and the release of VP4, which is locked
CC       onto the virion by VP7. During the virus exit from the host cell, VP4
CC       seems to be required to target the newly formed virions to the host
CC       cell lipid rafts.
CC   -!- SUBCELLULAR LOCATION: Outer capsid protein VP4: Virion. Host rough
CC       endoplasmic reticulum. Host cell membrane. Host cytoplasm, host
CC       cytoskeleton. Host endoplasmic reticulum-Golgi intermediate
CC       compartment. Note=The outer layer contains 180 copies of VP4, grouped
CC       as 60 dimers. Immature double-layered particles assembled in the
CC       cytoplasm bud across the membrane of the endoplasmic reticulum,
CC       acquiring during this process a transient lipid membrane that is
CC       modified with the ER resident viral glycoproteins NSP4 and VP7; these
CC       enveloped particles also contain VP4. As the particles move towards the
CC       interior of the ER cisternae, the transient lipid membrane and the non-
CC       structural protein NSP4 are lost, while the virus surface proteins VP4
CC       and VP7 rearrange to form the outermost virus protein layer, yielding
CC       mature infectious triple-layered particles. VP4 also seems to associate
CC       with lipid rafts of the host cell membrane probably for the exit of the
CC       virus from the infected cell by an alternate pathway.
CC   -!- DOMAIN: Outer capsid protein VP4: The VP4 spike is divided into a foot,
CC       a stalk and body, and a head.
CC   -!- PTM: Outer capsid protein VP4: Proteolytic cleavage by trypsin results
CC       in activation of VP4 functions and greatly increases infectivity. The
CC       penetration into the host cell is dependent on trypsin treatment of
CC       VP4. It produces two peptides, VP5* and VP8* that remain associated
CC       with the virion. Cleavage of VP4 by trypsin probably occurs in vivo in
CC       the lumen of the intestine prior to infection of enterocytes. Trypsin
CC       seems to be incorporated into the three-layered viral particles but
CC       remains inactive as long as the viral outer capsid is intact and would
CC       only be activated upon the solubilization of the latter.
CC   -!- MISCELLANEOUS: In group A rotaviruses, VP4 defines the P serotype.
CC   -!- MISCELLANEOUS: Some rotavirus strains are neuraminidase-sensitive and
CC       require sialic acid to attach to the cell surface. Some rotavirus
CC       strains are integrin-dependent. Some rotavirus strains depend on
CC       ganglioside for their entry into the host cell. Hsp70 also seems to be
CC       involved in the entry of some strains.
CC   -!- SIMILARITY: Belongs to the rotavirus VP4 family.
case <FTTag:cleavage1> and (<FTTag:cleavage2> or <FTTag:cleavage3>)
CC   -!- FUNCTION: Outer capsid protein VP5*: Forms the spike 'foot' and 'body'
CC       and acts as a membrane permeabilization protein that mediates release
CC       of viral particles from endosomal compartments into the cytoplasm.
CC       During entry, the part of VP5* that protrudes from the virus folds back
CC       on itself and reorganizes from a local dimer to a trimer. This
CC       reorganization may be linked to membrane penetration by exposing VP5*
CC       hydrophobic region. In integrin-dependent strains, VP5* targets the
CC       integrin heterodimer ITGA2/ITGB1 for cell attachment.
CC   -!- FUNCTION: Outer capsid protein VP8*: Forms the head of the spikes and
CC       mediates the recognition of specific host cell surface glycans. It is
CC       the viral hemagglutinin and an important target of neutralizing
CC       antibodies. In sialic acid-dependent strains, VP8* binds to host cell
CC       sialic acid, most probably a ganglioside, providing the initial
CC       contact. In some other strains, VP8* mediates the attachment to histo-
CC       blood group antigens (HBGAs) for viral entry.
CC   -!- SUBUNIT: Outer capsid protein VP4: Homotrimer. VP4 adopts a dimeric
CC       appearance above the capsid surface, while forming a trimeric base
CC       anchored inside the capsid layer. Only hints of the third molecule are
CC       observed above the capsid surface. It probably performs a series of
CC       molecular rearrangements during viral entry. Prior to trypsin cleavage,
CC       it is flexible. The priming trypsin cleavage triggers its rearrangement
CC       into rigid spikes with approximate two-fold symmetry of their
CC       protruding parts. After an unknown second triggering event, cleaved VP4
CC       may undergo another rearrangement, in which two VP5* subunits fold back
CC       on themselves and join a third subunit to form a tightly associated
CC       trimer, shaped like a folded umbrella. Outer capsid protein VP4:
CC       Interacts with VP6. Outer capsid protein VP4: Interacts with VP7. Outer
CC       capsid protein VP5*: Homotrimer. The trimer is coiled-coil stabilized
CC       by its C-terminus, however, its N-terminus, known as antigen domain or
CC       'body', seems to be flexible allowing it to self-associate either as a
CC       dimer or a trimer.
CC   -!- SUBCELLULAR LOCATION: Outer capsid protein VP8*: Virion. Note=Outer
CC       capsid protein.
CC   -!- SUBCELLULAR LOCATION: Outer capsid protein VP5*: Virion. Note=Outer
CC       capsid protein.
else case (<FTTag:cleavage2> or <FTTag:cleavage3>) and not <FTTag:cleavage1>
CC   -!- FUNCTION: Outer capsid protein VP5*: Forms the spike 'foot' and 'body'
CC       and acts as a membrane permeabilization protein that mediates release
CC       of viral particles from endosomal compartments into the cytoplasm.
CC       During entry, the part of VP5* that protrudes from the virus folds back
CC       on itself and reorganizes from a local dimer to a trimer. This
CC       reorganization may be linked to membrane penetration by exposing VP5*
CC       hydrophobic region. In integrin-dependent strains, VP5* targets the
CC       integrin heterodimer ITGA2/ITGB1 for cell attachment.
CC   -!- SUBUNIT: Outer capsid protein VP4: Homotrimer. VP4 adopts a dimeric
CC       appearance above the capsid surface, while forming a trimeric base
CC       anchored inside the capsid layer. Only hints of the third molecule are
CC       observed above the capsid surface. It probably performs a series of
CC       molecular rearrangements during viral entry. Prior to trypsin cleavage,
CC       it is flexible. The priming trypsin cleavage triggers its rearrangement
CC       into rigid spikes with approximate two-fold symmetry of their
CC       protruding parts. After an unknown second triggering event, cleaved VP4
CC       may undergo another rearrangement, in which two VP5* subunits fold back
CC       on themselves and join a third subunit to form a tightly associated
CC       trimer, shaped like a folded umbrella. Outer capsid protein VP4:
CC       Interacts with VP6. Outer capsid protein VP4: Interacts with VP7. Outer
CC       capsid protein VP5*: Homotrimer. The trimer is coiled-coil stabilized
CC       by its C-terminus, however, its N-terminus, known as antigen domain or
CC       'body', seems to be flexible allowing it to self-associate either as a
CC       dimer or a trimer.
CC   -!- SUBCELLULAR LOCATION: Outer capsid protein VP5*: Virion. Note=Outer
CC       capsid protein.
else case <FTTag:cleavage1> and not (<FTTag:cleavage2> or <FTTag:cleavage3>)
CC   -!- FUNCTION: Outer capsid protein VP8*: Forms the head of the spikes and
CC       mediates the recognition of specific host cell surface glycans. It is
CC       the viral hemagglutinin and an important target of neutralizing
CC       antibodies. In sialic acid-dependent strains, VP8* binds to host cell
CC       sialic acid, most probably a ganglioside, providing the initial
CC       contact. In some other strains, VP8* mediates the attachment to histo-
CC       blood group antigens (HBGAs) for viral entry.
CC   -!- SUBUNIT: Outer capsid protein VP4: Homotrimer. VP4 adopts a dimeric
CC       appearance above the capsid surface, while forming a trimeric base
CC       anchored inside the capsid layer. Only hints of the third molecule are
CC       observed above the capsid surface. It probably performs a series of
CC       molecular rearrangements during viral entry. Outer capsid protein VP4:
CC       Interacts with VP6. Outer capsid protein VP4: Interacts with VP7.
CC   -!- SUBCELLULAR LOCATION: Outer capsid protein VP8*: Virion. Note=Outer
CC       capsid protein.
end case
case <FTGroup:1>
CC   -!- MISCELLANEOUS: This strain probably uses sialic acid to attach to the
CC       host cell.
end case
XX
DR   Pfam; PF17477; Rota_VP4_MID; 1; trigger=no
DR   Pfam; PF00426; VP4_haemagglut; 1; trigger=no
DR   Pfam; PF17478; VP4_helical; 1; trigger=no
DR   General; Coiled_coil; -; 0-unlimited; trigger=yes
XX
KW   Capsid protein
case <FTTag:disulf>
KW   Disulfide bond
end case
KW   Hemagglutinin
KW   Host cell membrane
KW   Host cytoplasm
KW   Host cytoskeleton
KW   Host endoplasmic reticulum
KW   Host membrane
KW   Host-virus interaction
KW   Membrane
KW   Outer capsid protein
KW   Viral attachment to host cell
KW   Viral penetration into host cytoplasm
KW   Viral penetration via permeabilization of host membrane
KW   Virion
KW   Virus entry into host cell
XX
GO   GO:0044168; C:host cell rough endoplasmic reticulum
GO   GO:0039624; C:viral outer capsid
GO   GO:0039665; P:permeabilization of host organelle membrane involved in viral entry into host cell
GO   GO:0019062; P:virion attachment to host cell
XX
FT   From: VP4_ROTRH (P12473)
FT   CHAIN           Nter..Cter
FT                   /note="Outer capsid protein VP4"
FT   SITE            231..232
FT                   /note="Cleavage"
FT   Tag: cleavage1; Optional; Condition: [RT]-[NY]
FT   SITE            241..242
FT                   /note="Cleavage"
FT   Condition: R-[NASTDEQ]
FT   SITE            247..248
FT                   /note="Cleavage; associated with enhancement of
FT                   infectivity"
FT   Tag: cleavage2; Optional; Condition: [KR]-[AV]
case <FTTag:cleavage1>
FT   CHAIN           Nter..231
FT                   /note="Outer capsid protein VP8*"
end case
case <FTTag:cleavage2>
FT   CHAIN           248..Cter
FT                   /note="Outer capsid protein VP5*"
end case
FT   MOTIF           308..310
FT                   /note="DGE motif; interaction with ITGA2/ITGB1 heterodimer"
FT   Condition: D-G-E
FT   MOTIF           448..450
FT                   /note="YGL motif; interaction with ITGA4"
FT   Condition: Y-G-L
FT   MOTIF           644..646
FT                   /note="KID motif; interaction with HSPA8"
FT   Condition: K-I-D
FT   REGION          389..409
FT                   /note="Hydrophobic; possible role in virus entry into host
FT                   cell"
FT   REGION          65..224
FT                   /note="Spike head"
FT   REGION          248..479
FT                   /note="Spike body and stalk (antigen domain)"
FT   REGION          389..409
FT                   /note="Hydrophobic; possible role in virus entry into host
FT                   cell"
FT   REGION          510..776
FT                   /note="Spike foot"
FT   SITE            101
FT                   /note="Binding to sialic acid"
FT   Group: 1; Condition: R
FT   SITE            190
FT                   /note="Binding to sialic acid"
FT   Group: 1; Condition: S
FT   DISULFID        203..216
FT   Tag: disulf; Optional; Condition: C-x*-C
FT   DISULFID        318..380
FT   Tag: disulf; Optional; Condition: C-x*-C
FT   From: VP4_ROTBU (P12474)
FT   SITE            246..247
FT                   /note="Probable cleavage"
FT   Tag: cleavage3; Optional; Condition: [R]-[EIV]
case <FTTag:cleavage3>
FT   CHAIN           247..Cter
FT                   /note="Outer capsid protein VP5*"
end case
XX
Size: 770-780;
Related: MF_04125;
Template: P12473; Q96802; A2T3T2; P11193; Q04916;
Scope:
 Viruses; Rotavirus
Fusion:
 Nter: None
 Cter: None
Duplicate: None
Plasmid: None
Comments: None
XX
# Revision 1.9 2021/08/26
//