VP4_ROTGA
ID VP4_ROTGA Reviewed; 749 AA.
AC Q04916;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 02-DEC-2020, entry version 81.
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:0000305};
DE Contains:
DE RecName: Full=Outer capsid protein VP5* {ECO:0000305};
OS Rotavirus B (isolate RVB/Human/China/ADRV/1982) (RV-B) (Rotavirus B
OS (isolate adult diarrhea rotavirus)).
OC Viruses; Riboviria; Orthornavirae; Duplornaviricota; Resentoviricetes;
OC Reovirales; Reoviridae; Sedoreovirinae; Rotavirus.
OX NCBI_TaxID=10942;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8386274; DOI=10.1128/jvi.67.5.2730-2738.1993;
RA Mackow E.R., Werner-Eckert R., Fay M.E., Tao H., Chen G.-M.;
RT "Identification and baculovirus expression of the VP4 protein of the human
RT group B rotavirus ADRV.";
RL J. Virol. 67:2730-2738(1993).
RN [2]
RP PROTEOLYTIC CLEAVAGE.
RX PubMed=19774684; DOI=10.1002/jmv.21613;
RA Aung T.S., Kobayashi N., Nagashima S., Ghosh S., Aung M.S., Oo K.Y.,
RA Win N.;
RT "Detection of group B rotavirus in an adult with acute gastroenteritis in
RT Yangon, Myanmar.";
RL J. Med. Virol. 81:1968-1974(2009).
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:0000305}.
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:0000305}.
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:0000305}.
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:0000305}.
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 -!- 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; M91434; AAA47338.1; -; mRNA.
DR PIR; A45687; A45687.
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; IPR038017; Rota_VP4_MID_sf.
DR SUPFAM; SSF111379; SSF111379; 1.
PE 1: Evidence at protein level;
KW Capsid protein; 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..749
FT /note="Outer capsid protein VP4"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04125"
FT /id="PRO_0000149538"
FT CHAIN 1..206
FT /note="Outer capsid protein VP8*"
FT /id="PRO_0000369838"
FT CHAIN 214..749
FT /note="Outer capsid protein VP5*"
FT /id="PRO_0000369839"
FT SITE 206..207
FT /note="Probable cleavage"
FT /evidence="ECO:0000303|PubMed:19774684"
FT SITE 213..214
FT /note="Probable cleavage"
FT /evidence="ECO:0000303|PubMed:19774684"
SQ SEQUENCE 749 AA; 84362 MW; D1223527DEAE0F21 CRC64;
MLTYLRREWQ SFGETVTIKN TFNAQEDNNQ SGRKTDNRPV KTEGRYCYKA DVNRSKYYHD
VQGFSLGQSD LHIDPTQFIM YSGTISNGIS YVNQAPSCVQ LSLKFTPGNS SLIEDLHIEP
YKVEVLKIEH VGNVSRATLL SDIVSLSIAQ KKLLLYGFTQ LGIQGLTGDV VSVETKRIPT
PTQTNLLTIE DSMQCFTWDM NCANVRSTKQ DSRLIIYEQE DGFWKIVTET LSIKVKPYFK
AYGTMGGAFK NWLVDSGFEK YQHDLAYVRD GVTVNAHTIT YVNPSGKAGL QQDWRPATDY
NGQITVLQPG DGFSVWYYED KWQINQAIYA KNFQSDTRAQ GYLENVGTLK FKMNYIPAFA
EIRNKPGKVN YAYLNGGFAQ VDASGYTGMS IILNFVCTGE RFYASDNNSR VDNKITPFIS
YIGDYYTLSG GDFYRQGCCA GFAAGYDDVS PEHGITVSYT VMKPSDPDFI TGGENYGESI
TSDLEVSIRN LQDQINSIIA EMNIQQVTSA VFTAITNLGE LPGLFSNITK VFSKTKEALS
KLKSRKKTSP MPIAATSIID KTTVDVPNLT IVNKMPEEYE LGIIYNSMRT KKLIEQKKHD
FSTFTVATEV KLPYISKATN FSDQFMTSIS SRGITIGKSD IIQYDPMNNI LSAMNRKNAQ
IINYKIDPDL AHEVLSQMST NATRSLFSLN VRKQLHINNS FDTPTYGQLV ERILDDGQLL
DILGKLNPNS VEELFSEFLH RIQHQLREY
