VP4_ROTHY
ID VP4_ROTHY Reviewed; 776 AA.
AC Q06895;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 23-FEB-2022, entry version 104.
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/Israel/RO1845/1993/G3P5A[3]) (RV-A).
OC Viruses; Riboviria; Orthornavirae; Duplornaviricota; Resentoviricetes;
OC Reovirales; Reoviridae; Sedoreovirinae; Rotavirus; Rotavirus A.
OX NCBI_TaxID=79694;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8277285; DOI=10.1099/0022-1317-74-12-2771;
RA Isegawa Y., Nakagomi O., Hoshino Y., Aboudy Y., Shif I., Silberstein I.,
RA Nakagomi T., Ueda S., Sears J., Flores J.;
RT "A new serotype of the outer capsid protein VP4 shared by an unusual human
RT rotavirus strain Ro1845 and canine rotaviruses.";
RL J. Gen. Virol. 74:2771-2774(1993).
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: 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 -!- MISCELLANEOUS: This strain probably uses sialic acid to attach to the
CC host cell. {ECO:0000255|HAMAP-Rule:MF_04132}.
CC -!- SIMILARITY: Belongs to the rotavirus VP4 family. {ECO:0000255|HAMAP-
CC Rule:MF_04132}.
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DR EMBL; D14726; BAA03546.1; -; mRNA.
DR SMR; Q06895; -.
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; 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.
DR SUPFAM; SSF49899; SSF49899; 1.
PE 2: Evidence at transcript level;
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..776
FT /note="Outer capsid protein VP4"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132"
FT /id="PRO_0000041093"
FT CHAIN 1..231
FT /note="Outer capsid protein VP8*"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132"
FT /id="PRO_0000041094"
FT CHAIN 248..776
FT /note="Outer capsid protein VP5*"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132"
FT /id="PRO_0000041095"
FT REGION 65..224
FT /note="Spike head"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132"
FT REGION 248..479
FT /note="Spike body and stalk (antigen domain)"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132"
FT REGION 389..409
FT /note="Hydrophobic; possible role in virus entry into host
FT cell"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132"
FT REGION 510..776
FT /note="Spike foot"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132"
FT COILED 484..511
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132"
FT MOTIF 308..310
FT /note="DGE motif; interaction with ITGA2/ITGB1 heterodimer"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132"
FT MOTIF 448..450
FT /note="YGL motif; interaction with ITGA4"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132"
FT MOTIF 644..646
FT /note="KID motif; interaction with HSPA8"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132"
FT SITE 101
FT /note="Binding to sialic acid"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132"
FT SITE 190
FT /note="Binding to sialic acid"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132"
FT SITE 231..232
FT /note="Cleavage"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132"
FT SITE 241..242
FT /note="Cleavage"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132"
FT SITE 247..248
FT /note="Cleavage; associated with enhancement of
FT infectivity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132"
FT DISULFID 203..216
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132"
FT DISULFID 318..380
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132"
SQ SEQUENCE 776 AA; 86470 MW; 8988696C9A0FBE12 CRC64;
MASLIYRQLL TNSYTVNLSD EIQEIGSTKT QNTTINPGPF AQTGYAPVNW GPGETNDSTT
IEPVLDGPYQ PTSFNPPVGY WMLLSPTTAG VIVEGTNNTD RWLATILIEP NVTSQQRTYT
IFGVQEQITI ENTSQTQWRF VDVSKTTQNG SYSQYGPLLS TPKLYAVMKY GGRIHTYSGQ
TPNATTGYYS ATNYDSVNMT TFCDFYIIPR SEESKCTEYI NNGLPPIQNT RNIVPLALSA
RNVIPLKAQS NEDIVVSKTS LWKEMQYNRD ITIRFKFANS IVKSGGLGYK WSEISFKPAN
YQYTYMRDGE EVTAHTTCSV NGMNDFSFNG GSLPTDFVIS RYEVIKENSY VYIDYWDDSQ
AFRNMVYVRS LAANLNSVTC AGGDYNFALP VGQWPYMTGG AVSLHSAGVT LSTQFTDFVS
LNSLRFRFRL AVEEPSFAIM RTRVSGLYGL PAANPNNGRE YYEIAGRFSL ISLVPSNDNY
QTPIANSVTV RQDLERQLGE LREEFNALSQ EIAMSQLIDL ALLPLDMFSM FSGIKSTIDA
AKSIATNVMK KFKRSSLASS VSTLTDSLSD AASSVSRGSS IRSVGSSVSA WTDVSIQITD
VSSSVSSIST QTSTISRRLR LKEMATQTEG MNFDDISAAV LKTKIDKSIQ ISPTTLPDIV
TEASEKFIPN RAYRVINNDE VFEAGTDGRF FAYRVDTFEE IPFDVQKFAD LVTDSPVISA
IIDFKTLKNL NDNYGIGKQQ AFNLLRSDPR VLREFINQNN PIIRNRIEQL IMQCRL
