ID   A0A024CFA7_9REOV        Unreviewed;       775 AA.
AC   A0A024CFA7;
DT   09-JUL-2014, integrated into UniProtKB/TrEMBL.
DT   09-JUL-2014, sequence version 1.
DT   26-FEB-2020, entry version 33.
DE   RecName: Full=Outer capsid protein VP4 {ECO:0000256|HAMAP-Rule:MF_04125, ECO:0000256|SAAS:SAAS01200695};
DE   AltName: Full=Hemagglutinin {ECO:0000256|HAMAP-Rule:MF_04125};
GN   Name=VP4 {ECO:0000313|EMBL:AHZ33086.1};
GN   ORFNames=L312_46656gpVP4 {ECO:0000313|EMBL:AHZ33086.1};
OS   Rotavirus A.
OC   Viruses; Riboviria; Reoviridae; Sedoreovirinae; Rotavirus.
OX   NCBI_TaxID=28875 {ECO:0000313|EMBL:AHZ33086.1, ECO:0000313|Proteomes:UP000155231};
RN   [1] {ECO:0000313|EMBL:AHZ33086.1, ECO:0000313|Proteomes:UP000155231}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=RVA/Human-wt/ZAF/MRC-DPRU1052/2008/G1P[8]
RC   {ECO:0000313|EMBL:AHZ33086.1};
RA   Wentworth D.E., Halpin R.A., Stucker K.M., Akopov A., Fedorova N.,
RA   Tsitrin T., Puri V., Stockwell T., Amedeo P., Bishop B., Gupta N.,
RA   Hoover J., Katzel D., Schobel S., Shrivastava S., Nyaga M.M.,
RA   Magagula N.B., Peenze I., Seheri M.L., Mphahlele J., Steele A.D.,
RA   Mwenda M.J.;
RL   Submitted (APR-2014) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Forms the spike 'foot' and 'body' and acts as a membrane
CC       permeabilization protein that mediates release of viral particles from
CC       endosomal compartments into the cytoplasm. During entry, the part of
CC       VP5* that protrudes from the virus folds back on itself and reorganizes
CC       from a local dimer to a trimer. This reorganization may be linked to
CC       membrane penetration by exposing VP5* hydrophobic region. In integrin-
CC       dependent strains, VP5* targets the integrin heterodimer ITGA2/ITGB1
CC       for cell attachment. {ECO:0000256|SAAS:SAAS01238946}.
CC   -!- FUNCTION: Outer capsid protein VP4: Spike-forming protein that mediates
CC       virion attachment to the host epithelial cell receptors and plays a
CC       major role in cell penetration, determination of host range restriction
CC       and virulence. Rotavirus attachment and entry into the host cell
CC       probably involves multiple sequential contacts between the outer capsid
CC       proteins VP4 and VP7, and the cell receptors. It is subsequently lost,
CC       together with VP7, following virus entry into the host cell. Following
CC       entry into the host cell, low intracellular or intravesicular Ca(2+)
CC       concentration probably causes the calcium-stabilized VP7 trimers to
CC       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:0000256|HAMAP-Rule:MF_04125}.
CC   -!- SUBCELLULAR LOCATION: Host cell membrane
CC       {ECO:0000256|SAAS:SAAS01200690}. Host cytoplasm, host cytoskeleton
CC       {ECO:0000256|SAAS:SAAS01043062}. Host endoplasmic reticulum-Golgi
CC       intermediate compartment {ECO:0000256|SAAS:SAAS01200678}. Host rough
CC       endoplasmic reticulum {ECO:0000256|SAAS:SAAS01200666}. Virion
CC       {ECO:0000256|SAAS:SAAS01200667}.
CC   -!- SUBCELLULAR LOCATION: [Outer capsid protein VP4]: Virion
CC       {ECO:0000256|HAMAP-Rule:MF_04125}. Host rough endoplasmic reticulum
CC       {ECO:0000256|HAMAP-Rule:MF_04125}. Host cell membrane
CC       {ECO:0000256|HAMAP-Rule:MF_04125}. Host endoplasmic reticulum-Golgi
CC       intermediate compartment {ECO:0000256|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:0000256|HAMAP-Rule:MF_04125}.
CC   -!- DOMAIN: Outer capsid protein VP4: The VP4 spike is divided into a foot,
CC       a stalk and body, and a head. {ECO:0000256|HAMAP-Rule:MF_04125}.
CC   -!- PTM: Outer capsid protein VP4: Proteolytic cleavage by trypsin results
CC       in activation of VP4 functions and greatly increases infectivity. The
CC       penetration into the host cell is dependent on trypsin treatment of
CC       VP4. It produces two peptides, VP5* and VP8* that remain associated
CC       with the virion. Cleavage of VP4 by trypsin probably occurs in vivo in
CC       the lumen of the intestine prior to infection of enterocytes. Trypsin
CC       seems to be incorporated into the three-layered viral particles but
CC       remains inctive as long as the viral outer capsid is intact and would
CC       only be activated upon the solubilization of the latter.
CC       {ECO:0000256|HAMAP-Rule:MF_04125}.
CC   -!- SIMILARITY: Belongs to the rotavirus VP4 family. {ECO:0000256|HAMAP-
CC       Rule:MF_04125, ECO:0000256|SAAS:SAAS01200685}.
CC   -!- CAUTION: Lacks conserved residue(s) required for the propagation of
CC       feature annotation. {ECO:0000256|HAMAP-Rule:MF_04125}.
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DR   EMBL; KJ752276; AHZ33086.1; -; Genomic_RNA.
DR   Proteomes; UP000155231; 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_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 {ECO:0000256|HAMAP-Rule:MF_04125,
KW   ECO:0000256|SAAS:SAAS01200681};
KW   Cleavage on pair of basic residues {ECO:0000256|HAMAP-Rule:MF_04125};
KW   Coiled coil {ECO:0000256|HAMAP-Rule:MF_04125,
KW   ECO:0000256|SAAS:SAAS00976466};
KW   Disulfide bond {ECO:0000256|SAAS:SAAS00976472};
KW   Hemagglutinin {ECO:0000256|HAMAP-Rule:MF_04125,
KW   ECO:0000256|SAAS:SAAS01200694};
KW   Host cell membrane {ECO:0000256|HAMAP-Rule:MF_04125,
KW   ECO:0000256|SAAS:SAAS01200691};
KW   Host cytoplasm {ECO:0000256|SAAS:SAAS01043067};
KW   Host cytoskeleton {ECO:0000256|SAAS:SAAS01043063};
KW   Host endoplasmic reticulum {ECO:0000256|HAMAP-Rule:MF_04125,
KW   ECO:0000256|SAAS:SAAS01200665};
KW   Host membrane {ECO:0000256|HAMAP-Rule:MF_04125,
KW   ECO:0000256|SAAS:SAAS01200682};
KW   Host-virus interaction {ECO:0000256|HAMAP-Rule:MF_04125,
KW   ECO:0000256|SAAS:SAAS01200662};
KW   Membrane {ECO:0000256|HAMAP-Rule:MF_04125, ECO:0000256|SAAS:SAAS01200688};
KW   Outer capsid protein {ECO:0000256|HAMAP-Rule:MF_04125,
KW   ECO:0000256|SAAS:SAAS01200669};
KW   Viral attachment to host cell {ECO:0000256|HAMAP-Rule:MF_04125,
KW   ECO:0000256|SAAS:SAAS01200684};
KW   Viral penetration into host cytoplasm {ECO:0000256|HAMAP-Rule:MF_04125,
KW   ECO:0000256|SAAS:SAAS01200663};
KW   Viral penetration via permeabilization of host membrane {ECO:0000256|HAMAP-
KW   Rule:MF_04125, ECO:0000256|SAAS:SAAS01200668};
KW   Virion {ECO:0000256|HAMAP-Rule:MF_04125, ECO:0000256|SAAS:SAAS01200664};
KW   Virus entry into host cell {ECO:0000256|HAMAP-Rule:MF_04125,
KW   ECO:0000256|SAAS:SAAS01200683}.
FT   CHAIN           1..775
FT                   /note="Outer capsid protein VP4"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04125"
FT                   /id="PRO_5023354187"
FT   DOMAIN          249..473
FT                   /note="Rota_VP4_MID"
FT                   /evidence="ECO:0000259|Pfam:PF17477"
FT   DOMAIN          485..775
FT                   /note="VP4_helical"
FT                   /evidence="ECO:0000259|Pfam:PF17478"
FT   COILED          483..510
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04125"
SQ   SEQUENCE   775 AA;  87409 MW;  DCB7BF9CC9639466 CRC64;
     MASLIYRQLL TNSYSVDLYD EIKQIGSEKT QNVTVNPGPF AQTRYAPVNW GHGEINDSTT
     VEPILDGPYQ PTTFTPPTDY WILINSNTNG VVYESTNNSD FWTAVIAVEP HVNPVDRQYN
     VFGENKQFNV RNDSDKWKFL EMFRGSSQND FYNRRTLTSD TRLVGILKYG GRIWTFHGET
     PRATTDSSST ANLNGISITI HSEFYIIPRS QESKCNEYIN NGLPPIQNTR NVVPLSLSSR
     SIQYTRAQVN EDITISKTSL WKEMQYNRDI IIRFKFGNSI IKLGGLGYKW SEISYKAANY
     QYNYLRDGEQ VTAHTTCSVN GVNNFSYNGG SLPTDFSISR YEVIKENSYV YVDYWDDSKA
     FRNMVYVRSL AANLNSVKCT GGSYDFSIPV GAWPVMNGGA VSLHFAGVTL STQFTDFVSL
     NSLRFRFSLT VDEPSFSILR TRTVNLYGLP AANPNNGNEY YEISGRFSLI SLVPTNDDYQ
     TPIMNSVTVR QDLERQLTDL REEFNSLSQE IAMSQLIDLA LLPLDMFSMF SGIKSTIDLT
     KSMATSVMKK FRKSKLATSV SEMTNSLSDA ASSASRSVSV RSNVSAFSNW TNVSNDVSNV
     TNSVNDISTQ TSTISKNLRL KEMITQTEGM SFDDISAAVL KTKIDMSTQI GKNTLPDIVT
     EASEKFIPKR SYRILKDDEV MEINTEGKFF AYKIDTLNEV PFDVNKFAEL VTNSPVISAI
     IDFKTLKNLN DNYGITRIEA LNLIKSNPNV LRNFINQNNP IIRNRIEQLI LQCKL
//