VP4_ROTHC
ID VP4_ROTHC Reviewed; 744 AA.
AC Q82040;
DT 14-APR-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 02-JUN-2021, entry version 94.
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/Human/United Kingdom/Bristol/1989) (RV-C).
OC Viruses; Riboviria; Orthornavirae; Duplornaviricota; Resentoviricetes;
OC Reovirales; Reoviridae; Sedoreovirinae; Rotavirus.
OX NCBI_TaxID=31567;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA], AND PROTEOLYTIC CLEAVAGE (OUTER CAPSID
RP PROTEIN VP4).
RX PubMed=8091676; DOI=10.1006/viro.1994.1551;
RA Fielding P.A., Lambden P.R., Caul E.O., Clarke I.N.;
RT "Molecular characterization of the outer capsid spike protein (VP4) gene
RT from human group C rotavirus.";
RL Virology 204:442-446(1994).
RN [2]
RP PROTEOLYTIC CLEAVAGE (OUTER CAPSID PROTEIN VP4).
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: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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X79442; CAA55958.1; -; Genomic_RNA.
DR PIR; S45061; S45061.
DR RefSeq; YP_392514.1; NC_007572.1.
DR PDB; 5ZHG; X-ray; 1.80 A; A=64-224.
DR PDB; 5ZHO; X-ray; 1.40 A; A=64-224.
DR PDBsum; 5ZHG; -.
DR PDBsum; 5ZHO; -.
DR SMR; Q82040; -.
DR UniLectin; Q82040; -.
DR PRIDE; Q82040; -.
DR GeneID; 3773132; -.
DR KEGG; vg:3773132; -.
DR Proteomes; UP000007664; 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 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 1: Evidence at protein level;
KW 3D-structure; Capsid protein; Coiled coil; Hemagglutinin;
KW Host cell membrane; Host endoplasmic reticulum; Host membrane;
KW Host-virus interaction; Membrane; Outer capsid protein; Reference proteome;
KW Viral attachment to host cell; Viral penetration into host cytoplasm;
KW Viral penetration via permeabilization of host membrane; Virion;
KW Virus entry into host cell.
FT CHAIN 1..744
FT /note="Outer capsid protein VP4"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04125"
FT /id="PRO_0000369876"
FT CHAIN 1..231
FT /note="Outer capsid protein VP8*"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04125"
FT /id="PRO_0000369877"
FT CHAIN 248..744
FT /note="Outer capsid protein VP5*"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04125"
FT /id="PRO_0000369878"
FT REGION 396..413
FT /note="Hydrophobic; possible role in virus entry into host
FT cell"
FT /evidence="ECO:0000269|PubMed:18814255"
FT COILED 503..523
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04125"
FT SITE 231..232
FT /note="Cleavage"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04125,
FT ECO:0000305|PubMed:18814255, ECO:0000305|PubMed:8091676"
FT SITE 247..248
FT /note="Cleavage"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04125,
FT ECO:0000305|PubMed:18814255, ECO:0000305|PubMed:8091676"
FT STRAND 64..69
FT /evidence="ECO:0007829|PDB:5ZHO"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:5ZHO"
FT HELIX 76..78
FT /evidence="ECO:0007829|PDB:5ZHO"
FT STRAND 80..82
FT /evidence="ECO:0007829|PDB:5ZHO"
FT STRAND 84..89
FT /evidence="ECO:0007829|PDB:5ZHO"
FT STRAND 95..101
FT /evidence="ECO:0007829|PDB:5ZHO"
FT STRAND 111..117
FT /evidence="ECO:0007829|PDB:5ZHO"
FT STRAND 122..124
FT /evidence="ECO:0007829|PDB:5ZHO"
FT TURN 127..130
FT /evidence="ECO:0007829|PDB:5ZHO"
FT HELIX 134..136
FT /evidence="ECO:0007829|PDB:5ZHO"
FT STRAND 137..139
FT /evidence="ECO:0007829|PDB:5ZHO"
FT STRAND 141..151
FT /evidence="ECO:0007829|PDB:5ZHO"
FT STRAND 154..162
FT /evidence="ECO:0007829|PDB:5ZHO"
FT STRAND 165..176
FT /evidence="ECO:0007829|PDB:5ZHO"
FT STRAND 179..190
FT /evidence="ECO:0007829|PDB:5ZHO"
FT TURN 191..193
FT /evidence="ECO:0007829|PDB:5ZHO"
FT STRAND 194..205
FT /evidence="ECO:0007829|PDB:5ZHO"
FT STRAND 213..215
FT /evidence="ECO:0007829|PDB:5ZHO"
FT STRAND 219..223
FT /evidence="ECO:0007829|PDB:5ZHO"
SQ SEQUENCE 744 AA; 84081 MW; 96A9DBACBB7CD449 CRC64;
MASSLYAQLI SQNYYSLGNE ILSDQQTNKV VSDYVDAGNY TYAQLPPTTW GSGSILKSAF
STPEITGPHT NTVIEWSNLI NTNTWLLYQK PLNSVRLLKH GPDTYNSNLA AFELWYGKSG
TTITSVYYNT INNQNKTHDA NSDCLILFWN EGSTQLEKQV VTFNWNVGGI LIKPINSSRM
RICMSGMENF NNDSFNWENW NHEFPRSNPG ININMYTEYF LASSDPYTYL KNLQQPTAKT
VDMKMMKKMN DNSKLGDGPI NVSNIISKDS LWQEVQYVRD ITLQCKILSE IVKGGGWGYD
YTSVTFKTVN HTYSYTRAGE NVNAHVTISF NNVKERAYGG SLPTDFKIGR FDILDTDSYV
YIDYWDDSEI FKNMVYVRDV RADIGGFQYS YSSEMSYYFQ IPVGSYPGLH SSRLQLVYDR
CLLSQQFTDY AALNSLRFVF RVVSTSGWFI TTGDINTRRV ASGTGFAYSD GHVANTVGTI
SFISLIPSNP NYQTPIASSS TVRMDLERKI NDLRDDFNAL ASSVALSDIL SLAMSPLTFS
NLLESVPAIT SSVKDVAASV MKKFRSTKMF KKAAKQNYRE FVIGDLLEDV TNVARNNNSL
NYSDITSAMM VSTTNRLQIT DVDTFSEIVS RSADNFISNR SYRMIENNTV HEITPTRRFS
YDIKTLQQRN FDIDKFSKLA SQSPVISAIV DFATIKAIRD TYGISDDIIY KLVASDAPTI
LSFINQNNPL IRNRITNLIN QCKL
