VP4_ROTWI
ID VP4_ROTWI Reviewed; 775 AA.
AC B3SRX5;
DT 14-APR-2009, integrated into UniProtKB/Swiss-Prot.
DT 02-SEP-2008, sequence version 1.
DT 03-AUG-2022, entry version 58.
DE RecName: Full=Outer capsid protein VP4 {ECO:0000255|HAMAP-Rule:MF_04132};
DE AltName: Full=Hemagglutinin {ECO:0000255|HAMAP-Rule:MF_04132};
DE Contains:
DE RecName: Full=Outer capsid protein VP8* {ECO:0000255|HAMAP-Rule:MF_04132};
DE Contains:
DE RecName: Full=Outer capsid protein VP5* {ECO:0000255|HAMAP-Rule:MF_04132};
OS Rotavirus A (isolate RVA/Human/United States/WI61/1983/G9P1A[8]) (RV-A).
OC Viruses; Riboviria; Orthornavirae; Duplornaviricota; Resentoviricetes;
OC Reovirales; Reoviridae; Sedoreovirinae; Rotavirus; Rotavirus A.
OX NCBI_TaxID=578830;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=18786998; DOI=10.1128/jvi.01402-08;
RA Heiman E.M., McDonald S.M., Barro M., Taraporewala Z.F., Bar-Magen T.,
RA Patton J.T.;
RT "Group A human rotavirus genomics: evidence that gene constellations are
RT influenced by viral protein interactions.";
RL J. Virol. 82:11106-11116(2008).
RN [2]
RP REVIEW.
RX PubMed=16575520; DOI=10.1007/s10719-006-5435-y;
RA Isa P., Arias C.F., Lopez S.;
RT "Role of sialic acids in rotavirus infection.";
RL Glycoconj. J. 23:27-37(2006).
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. During the virus exit from the host cell, VP4
CC seems to be required to target the newly formed virions to the host
CC cell lipid rafts. {ECO:0000255|HAMAP-Rule:MF_04132}.
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 by exposing
CC VP5* hydrophobic region. In integrin-dependent strains, VP5* targets
CC the integrin heterodimer ITGA2/ITGB1 for cell attachment.
CC {ECO:0000255|HAMAP-Rule:MF_04132}.
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. In sialic acid-dependent strains, VP8* binds to host cell
CC sialic acid, most probably a ganglioside, providing the initial
CC contact. In some other strains, VP8* mediates the attachment to histo-
CC blood group antigens (HBGAs) for viral entry. {ECO:0000255|HAMAP-
CC Rule:MF_04132}.
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_04132}.
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_04132}.
CC -!- SUBCELLULAR LOCATION: [Outer capsid protein VP4]: Virion
CC {ECO:0000255|HAMAP-Rule:MF_04132}. Host rough endoplasmic reticulum
CC {ECO:0000255|HAMAP-Rule:MF_04132}. Host cell membrane
CC {ECO:0000255|HAMAP-Rule:MF_04132}. Host cytoplasm, host cytoskeleton
CC {ECO:0000255|HAMAP-Rule:MF_04132}. Host endoplasmic reticulum-Golgi
CC intermediate compartment {ECO:0000255|HAMAP-Rule:MF_04132}. 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. VP4 also seems to associate with lipid rafts of the
CC host cell membrane probably for the exit of the virus from the infected
CC cell by an alternate pathway. {ECO:0000255|HAMAP-Rule:MF_04132}.
CC -!- SUBCELLULAR LOCATION: [Outer capsid protein VP8*]: Virion
CC {ECO:0000255|HAMAP-Rule:MF_04132}. Note=Outer capsid protein.
CC {ECO:0000255|HAMAP-Rule:MF_04132}.
CC -!- SUBCELLULAR LOCATION: [Outer capsid protein VP5*]: Virion
CC {ECO:0000255|HAMAP-Rule:MF_04132}. Note=Outer capsid protein.
CC {ECO:0000255|HAMAP-Rule:MF_04132}.
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_04132}.
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_04132}.
CC -!- MISCELLANEOUS: This strain probably does not use sialic acid to attach
CC to the host cell. {ECO:0000303|PubMed:16575520}.
CC -!- MISCELLANEOUS: In group A rotaviruses, VP4 defines the P serotype.
CC {ECO:0000255|HAMAP-Rule:MF_04132}.
CC -!- MISCELLANEOUS: Some rotavirus strains are neuraminidase-sensitive and
CC require sialic acid to attach to the cell surface. Some rotavirus
CC strains are integrin-dependent. Some rotavirus strains depend on
CC ganglioside for their entry into the host cell. Hsp70 also seems to be
CC involved in the entry of some strains. {ECO:0000255|HAMAP-
CC Rule:MF_04132}.
CC -!- SIMILARITY: Belongs to the rotavirus VP4 family. {ECO:0000255|HAMAP-
CC Rule:MF_04132}.
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DR EMBL; EF672619; ABV53300.1; -; Genomic_RNA.
DR SMR; B3SRX5; -.
DR PRIDE; B3SRX5; -.
DR Proteomes; UP000006580; 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:0044163; C:host cytoskeleton; 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_04132; Rota_A_VP4; 1.
DR HAMAP; MF_04125; Rota_VP4; 1.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR InterPro; IPR042546; Rota_A_VP4.
DR InterPro; IPR035330; Rota_VP4_MID.
DR InterPro; IPR038017; Rota_VP4_MID_sf.
DR InterPro; IPR035329; VP4_helical.
DR Pfam; PF17477; Rota_VP4_MID; 1.
DR Pfam; PF17478; VP4_helical; 1.
DR SUPFAM; SSF111379; SSF111379; 1.
DR SUPFAM; SSF49899; SSF49899; 1.
PE 3: Inferred from homology;
KW Capsid protein; Coiled coil; Disulfide bond; Hemagglutinin;
KW Host cell membrane; Host cytoplasm; Host cytoskeleton;
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..775
FT /note="Outer capsid protein VP4"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132"
FT /id="PRO_0000368113"
FT CHAIN 1..230
FT /note="Outer capsid protein VP8*"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132"
FT /id="PRO_0000368114"
FT CHAIN 247..775
FT /note="Outer capsid protein VP5*"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132"
FT /id="PRO_0000368115"
FT REGION 65..223
FT /note="Spike head"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132"
FT REGION 247..478
FT /note="Spike body and stalk (antigen domain)"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132"
FT REGION 388..408
FT /note="Hydrophobic; possible role in virus entry into host
FT cell"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132"
FT REGION 509..775
FT /note="Spike foot"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132"
FT COILED 483..510
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132"
FT MOTIF 307..309
FT /note="DGE motif; interaction with ITGA2/ITGB1 heterodimer"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132"
FT MOTIF 447..449
FT /note="YGL motif; interaction with ITGA4"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132"
FT MOTIF 643..645
FT /note="KID motif; interaction with HSPA8"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132"
FT SITE 230..231
FT /note="Cleavage"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132"
FT SITE 240..241
FT /note="Cleavage"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132"
FT SITE 246..247
FT /note="Cleavage; associated with enhancement of
FT infectivity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132"
FT DISULFID 317..379
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132"
SQ SEQUENCE 775 AA; 87376 MW; 2A827F1C5C695822 CRC64;
MASLIYRQLL TNSYSVDLHD EIEQIGSEKT QNVTVNPGPF AQTRYAPVNW GHGEINDSTT
VEPILDGPYQ PTTFTPPIDY WILINSNTNG VVYESTNNSD FWTAVVAVEP HVNPVDRQYT
VFGENKQFNV RNDSDKWKFL EMFRSSSQNE FYNRRTLTSH TKLVGILKYG GRIWTFHGET
PRATTDSSNT ANLNDISIIV HSEFYIIPRS QESKCNEYIN NGLPPIQNTR NVVPLSLSSR
SIQYKRAQVN EDITISKTSL WKEMQYNSDI IIRFKFGNSI VKLGGLGYKW SEISFKAANY
QYNYLRDGEQ VTAHTTCSVN GVNNFSYNGG SLPTDFSVSR YEVIKENSYV YVDYWDDSKA
FRNMVYVRSL AANLNSVKCT GGSYNFSLPV GAWPVMNGGA VSLHFAGVTL STQFTDFVSL
NSLRFRFSLT VDEPSFSILR TRTVNLYGLP AANPNNGNEY YEISGRFSLI SLVPTNDDYQ
TPIMNSVTVR QDLERQLTDL REEFNSLSQE IAMSQLIDLA LLPLDMFSMF SGIKSTIDLT
KSMATSVMKK FRKSKLATSI SEMTNSLSDA ASSASRSVSI RSNISTISNL TNVSNDVSNV
TNSLNDISTQ TSTISKKLRL REMITQTEGM SFDDISAAVL KTKIDMSTQI GKNTLPDIVT
EASEKFIPKR SYRILKDDEV MEINTEGKVF AYKIDTLNEV PFDVNKFAEL VTNSPVISAI
IDFKTLKNLN DNYGITRIEA LNLIKSNPNV LRNFINQNNP IIRNRIEQLI LQCKL
