VP4_ROTBS
ID VP4_ROTBS Reviewed; 733 AA.
AC Q65525;
DT 14-APR-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 02-JUN-2021, entry version 77.
DE RecName: Full=Outer capsid protein VP4 {ECO:0000255|HAMAP-Rule:MF_04125};
DE AltName: Full=Hemagglutinin {ECO:0000255|HAMAP-Rule:MF_04125};
DE Contains:
DE RecName: Full=Outer capsid protein VP8* {ECO:0000255|HAMAP-Rule:MF_04125};
DE Contains:
DE RecName: Full=Outer capsid protein VP5* {ECO:0000255|HAMAP-Rule:MF_04125};
OS Rotavirus C (isolate RVC/Cow/Japan/Shintoku/1991/G2P[3]) (RV-C).
OC Viruses; Riboviria; Orthornavirae; Duplornaviricota; Resentoviricetes;
OC Reovirales; Reoviridae; Sedoreovirinae; Rotavirus.
OX NCBI_TaxID=33723;
OH NCBI_TaxID=9913; Bos taurus (Bovine).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Jiang B., Gentsch J.R., Tsunemitsu H., Saif L.J., Glass R.I.;
RT "Sequence analysis of VP3 and VP4 genes of a bovine group C rotavirus:
RT molecular evidence for a new P type.";
RL Submitted (MAY-1995) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: [Outer capsid protein VP4]: Spike-forming protein that
CC mediates virion attachment to the host epithelial cell receptors and
CC plays a major role in cell penetration, determination of host range
CC restriction and virulence. Rotavirus attachment and entry into the host
CC cell probably involves multiple sequential contacts between the outer
CC capsid proteins VP4 and VP7, and the cell receptors. It is subsequently
CC lost, together with VP7, following virus entry into the host cell.
CC Following entry into the host cell, low intracellular or intravesicular
CC Ca(2+) concentration probably causes the calcium-stabilized VP7 trimers
CC to 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. {ECO:0000255|HAMAP-Rule:MF_04125}.
CC -!- FUNCTION: [Outer capsid protein VP5*]: Forms the spike 'foot' and
CC 'body' and acts as a membrane permeabilization protein that mediates
CC release of viral particles from endosomal compartments into the
CC cytoplasm. During entry, the part of VP5* that protrudes from the virus
CC folds back on itself and reorganizes from a local dimer to a trimer.
CC This reorganization may be linked to membrane penetration.
CC {ECO:0000255|HAMAP-Rule:MF_04125}.
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. {ECO:0000255|HAMAP-Rule:MF_04125}.
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. Interacts with VP6. Interacts
CC with VP7. {ECO:0000255|HAMAP-Rule:MF_04125}.
CC -!- SUBUNIT: [Outer capsid protein VP5*]: Homotrimer. The trimer is coiled-
CC coil stabilized by its C-terminus, however, its N-terminus, known as
CC antigen domain or 'body', seems to be flexible allowing it to self-
CC associate either as a dimer or a trimer. {ECO:0000255|HAMAP-
CC Rule:MF_04125}.
CC -!- SUBCELLULAR LOCATION: [Outer capsid protein VP4]: Virion
CC {ECO:0000255|HAMAP-Rule:MF_04125}. Host rough endoplasmic reticulum
CC {ECO:0000255|HAMAP-Rule:MF_04125}. Host cell membrane
CC {ECO:0000255|HAMAP-Rule:MF_04125}. Host endoplasmic reticulum-Golgi
CC intermediate compartment {ECO:0000255|HAMAP-Rule:MF_04125}. Note=The
CC outer layer contains 180 copies of VP4, grouped as 60 dimers. Immature
CC double-layered particles assembled in the cytoplasm bud across the
CC membrane of the endoplasmic reticulum, acquiring during this process a
CC transient lipid membrane that is modified with the ER resident viral
CC glycoproteins NSP4 and VP7; these enveloped particles also contain VP4.
CC As the particles move towards the interior of the ER cisternae, the
CC transient lipid membrane and the non-structural protein NSP4 are lost,
CC while the virus surface proteins VP4 and VP7 rearrange to form the
CC outermost virus protein layer, yielding mature infectious triple-
CC layered particles. {ECO:0000255|HAMAP-Rule:MF_04125}.
CC -!- SUBCELLULAR LOCATION: [Outer capsid protein VP8*]: Virion
CC {ECO:0000255|HAMAP-Rule:MF_04125}. Note=Outer capsid protein.
CC {ECO:0000255|HAMAP-Rule:MF_04125}.
CC -!- SUBCELLULAR LOCATION: [Outer capsid protein VP5*]: Virion
CC {ECO:0000255|HAMAP-Rule:MF_04125}. Note=Outer capsid protein.
CC {ECO:0000255|HAMAP-Rule:MF_04125}.
CC -!- DOMAIN: [Outer capsid protein VP4]: The VP4 spike is divided into a
CC foot, a stalk and body, and a head. {ECO:0000255|HAMAP-Rule:MF_04125}.
CC -!- PTM: [Outer capsid protein VP4]: Proteolytic cleavage by trypsin
CC results in activation of VP4 functions and greatly increases
CC infectivity. The penetration into the host cell is dependent on trypsin
CC treatment of VP4. It produces two peptides, VP5* and VP8* that remain
CC associated with the virion. Cleavage of VP4 by trypsin probably occurs
CC in vivo in the lumen of the intestine prior to infection of
CC enterocytes. Trypsin seems to be incorporated into the three-layered
CC viral particles but remains inactive as long as the viral outer capsid
CC is intact and would only be activated upon the solubilization of the
CC latter. {ECO:0000255|HAMAP-Rule:MF_04125}.
CC -!- SIMILARITY: Belongs to the rotavirus VP4 family. {ECO:0000255|HAMAP-
CC Rule:MF_04125}.
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DR EMBL; U26551; AAB01672.1; -; Genomic_DNA.
DR SMR; Q65525; -.
DR GO; GO:0044172; C:host cell endoplasmic reticulum-Golgi intermediate compartment; IEA:UniProtKB-SubCell.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0044168; C:host cell rough endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0039624; C:viral outer capsid; IEA:UniProtKB-UniRule.
DR GO; GO:0039665; P:permeabilization of host organelle membrane involved in viral entry into host cell; IEA:UniProtKB-UniRule.
DR GO; GO:0099008; P:viral entry via permeabilization of inner membrane; IEA:UniProtKB-KW.
DR GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR HAMAP; MF_04125; Rota_VP4; 1.
DR InterPro; IPR042546; Rota_A_VP4.
DR InterPro; IPR035330; Rota_VP4_MID.
DR InterPro; IPR038017; Rota_VP4_MID_sf.
DR InterPro; IPR000416; VP4_concanavalin-like.
DR InterPro; IPR035329; VP4_helical.
DR Pfam; PF17477; Rota_VP4_MID; 1.
DR Pfam; PF00426; VP4_haemagglut; 1.
DR Pfam; PF17478; VP4_helical; 1.
DR SUPFAM; SSF111379; SSF111379; 1.
PE 3: Inferred from homology;
KW Capsid protein; Coiled coil; Hemagglutinin; Host cell membrane;
KW Host endoplasmic reticulum; Host membrane; Host-virus interaction;
KW Membrane; Outer capsid protein; Viral attachment to host cell;
KW Viral penetration into host cytoplasm;
KW Viral penetration via permeabilization of host membrane; Virion;
KW Virus entry into host cell.
FT CHAIN 1..733
FT /note="Outer capsid protein VP4"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04125"
FT /id="PRO_0000369873"
FT CHAIN 1..228
FT /note="Outer capsid protein VP8*"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04125"
FT /id="PRO_0000369874"
FT CHAIN 229..733
FT /note="Outer capsid protein VP5*"
FT /evidence="ECO:0000250, ECO:0000255|HAMAP-Rule:MF_04125"
FT /id="PRO_0000369875"
FT COILED 492..512
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04125"
FT SITE 228..229
FT /note="Cleavage"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04125"
FT SITE 244..245
FT /note="Cleavage"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04125"
SQ SEQUENCE 733 AA; 82495 MW; 67C1B19AFCD1631C CRC64;
MASSLYRQLI SQNYYSTGNE ILLDQQTNKT TVDYVDAGNY TYAQLPPTTW GAESTYESAF
SAPEITGPYT NTVIKLSDLS DSNVWVLYQK PTSTVKLLKN GPESYSWNLA AFELWYGKAN
TTVTSDYYSG MTNSEKSVEV DHDSLVLFWN EGSTALSNKV INFSWNVGGV LIKLTSNTRI
DICMANMDNF TSDSFNWEEW THNFPRSASM NIYTDYYLAS VDPYSQIRAL QQPIITTVEM
KMVKVKREGS INVDEVVSKD SLWQEVRYVR DITLQCKIES EVVKGGGWGY DYTSVAFKTI
NHTYSYTRAG EAVNAHVTIS FNNLKERSYG GSLPTDFKIG RFDIIDVDTY MYIDYWDDSE
IFKNMVYVRD LRADMGGFNY SSAMSYYFRI PVGQYPGLHS SGVRFTYERS LLSQQFTDQV
ALNSMRFVFR ATSSDGWFMT AGNINARRIA SGTGFAYSDG YVTETVGTVS FISLIPSNPN
YQTPIASSST VRMDLERKIN DLRNDFNELA SSVALGDILS LAMSPLTFAN LLESVPAIAS
SVKDVAANVM KKFKTTKMFK KAAKPKYKEY IIGDLLEDVT NLPRSTTAMD FDDITSAVMV
STTNRLQLTD VETLSEIVAR SADDFIPNRA YRMIEDGMVH EATPNGVFSY DLATLQQRNF
DMEKFMQLAS KSPVISAIVD FATLKAMRDT YGVSTDIMYK LVASDAPTIV SFINNNNPLI
RNRIEGLLRQ CRI
