ID   VP4_ROTB2               Reviewed;         826 AA.
AC   A9Q1L0;
DT   14-APR-2009, integrated into UniProtKB/Swiss-Prot.
DT   05-FEB-2008, sequence version 1.
DT   27-MAR-2024, entry version 61.
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 X (isolate RVX/Human/Bangladesh/NADRV-B219/2002/GXP[X]) (RV
OS   ADRV-N) (Rotavirus (isolate novel adult diarrhea rotavirus-B219)).
OC   Viruses; Riboviria; Orthornavirae; Duplornaviricota; Resentoviricetes;
OC   Reovirales; Sedoreoviridae; Rotavirus.
OX   NCBI_TaxID=348136;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND PUTATIVE CLEAVAGE SITES.
RX   PubMed=18814255; DOI=10.1002/jmv.21286;
RA   Nagashima S., Kobayashi N., Ishino M., Alam M.M., Ahmed M.U., Paul S.K.,
RA   Ganesh B., Chawla-Sarkar M., Krishnan T., Naik T.N., Wang Y.-H.;
RT   "Whole genomic characterization of a human rotavirus strain B219 belonging
RT   to a novel group of the genus Rotavirus.";
RL   J. Med. Virol. 80:2023-2033(2008).
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; EF453358; ABR32125.1; -; mRNA.
DR   IntAct; A9Q1L0; 1.
DR   Proteomes; UP000174021; Genome.
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   Pfam; PF17477; Rota_VP4_MID; 1.
DR   SUPFAM; SSF111379; VP4 membrane interaction domain; 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..826
FT                   /note="Outer capsid protein VP4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04125"
FT                   /id="PRO_0000369842"
FT   CHAIN           1..249
FT                   /note="Outer capsid protein VP8*"
FT                   /id="PRO_0000369843"
FT   CHAIN           263..826
FT                   /note="Outer capsid protein VP5*"
FT                   /id="PRO_0000369844"
FT   SITE            249..250
FT                   /note="Probable cleavage"
FT                   /evidence="ECO:0000305"
FT   SITE            262..263
FT                   /note="Probable cleavage"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   826 AA;  93311 MW;  B8CC3EDD7D540505 CRC64;
     MSLRSLLITT EAVGETTQTS DHQTSFSTRT YNEINDRPSL RVEKDGEKAY CFKNLDPVRY
     DTRMGEYPFD YGGQSTENNQ LQFDLFTKDL MADTDIGLSD DVRDDLKRQI KEYYQQGYRA
     IFLIRPQNQE QQYIASYSST NLNFTSQLSV GVNLSVLNKI QENKLHIYST QPHIPSVGCE
     MITKIFRTDV DNENSLINYS VPVTVTISVT KATFEDTFVW NQNNDYPNMN YKDLIPAVTK
     NSIYHDVKRI TKIHEYINSK KKKNGVGKIG GIQIAESKDG FWKILTKNYQ IKLKFGIEGY
     GVMGGTFGNW LIDSGFKTVE TNYEYQRNGK TINATTVASV KPSRKCGTRS PVFGQLQFSG
     EMMVLSHNDI LTVFYTEREW ALSNAIYAKN FATDFKRQFE VTAQSDELLV RTNVVPHTIK
     NTPGKALMEY SHGGFGQIDT SDYTGMALTF RFRCVSEDLP EGYYDKDKAL TFANVGLTSF
     QDRQETNGTY WVYNTSTVGF GSCYPKKEFE YDINVTYTTL LPSDPEFTTG GTNYAQSVTA
     VLEESFINLQ NQVNEMLTRM NISDLTSGVM SVFSVATSFP QILDGISDLL KAASSAFKKV
     KGKVGNVAKR LRGKRYVRLF DEDISIEETP RFLDSIRSSR RPSILSNMFN DDETFTALHT
     LASRTNSVAS DVTYIQPIIT TRIANSTPPV IAPASSVTYA KLKDISKIIN AEIDPKSIME
     FNQVSNTISI LDSTKKLAQY AVDPDVIDGI LNKMVGGHAR SLFSLKVRKH LLDAVEKDAF
     VKYNYHDLMG KLLNDRELLD ITNNLSSQKQ FELAKEFRDL LINALA
//