AC MF_04125; DC Protein; auto TR HAMAP; MF_04125; -; 1; level=0 XX Names: Rota_VP4 XX ID VP4 case and 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 and not DE RecName: Full=Outer capsid protein VP4; DE AltName: Full=Hemagglutinin; DE Contains: DE RecName: Full=Outer capsid protein VP8*; else case and not 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. CC -!- SUBCELLULAR LOCATION: Outer capsid protein VP4: Virion. Host rough CC endoplasmic reticulum. Host cell membrane. Host endoplasmic reticulum- CC Golgi intermediate compartment. Note=The outer layer contains 180 CC copies of VP4, grouped as 60 dimers. Immature double-layered particles CC assembled in the cytoplasm bud across the membrane of the endoplasmic CC reticulum, acquiring during this process a transient lipid membrane CC that is modified with the ER resident viral glycoproteins NSP4 and VP7; CC these enveloped particles also contain VP4. As the particles move CC towards the interior of the ER cisternae, the transient lipid membrane CC and the non-structural protein NSP4 are lost, while the virus surface CC proteins VP4 and VP7 rearrange to form the outermost virus protein CC layer, yielding mature infectious triple-layered particles. 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 -!- SIMILARITY: Belongs to the rotavirus VP4 family. case and 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. 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. 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 and not 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. 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 and not 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. 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 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; -; 1-unlimited; trigger=yes XX KW Capsid protein KW Cleavage on pair of basic residues KW Hemagglutinin KW Host cell membrane 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_ROTHC (Q82040) FT CHAIN Nter..Cter FT /note="Outer capsid protein VP4" FT SITE 231..232 FT /note="Cleavage" FT Tag: cleavage1; Optional; Condition: [KR]-[DEANST] FT SITE 247..248 FT /note="Cleavage" FT Tag: cleavage2; Optional; Condition: [KR]-[KATIVL] case FT CHAIN Nter..231 FT /note="Outer capsid protein VP8*" end case case FT CHAIN 248..Cter FT /note="Outer capsid protein VP5*" end case XX Size: 729-830; Related: MF_04132!; Template: Q82040; P12473; Q96802; A2T3T2; P11193; Scope: Viruses; Rotavirus Fusion: Nter: None Cter: None Duplicate: None Plasmid: None Comments: None XX # Revision 1.6 2020/02/06 //