ID   A0A024CFA7_9REOV        Unreviewed;       775 AA.
AC   A0A024CFA7;
DT   09-JUL-2014, integrated into UniProtKB/TrEMBL.
DT   09-JUL-2014, sequence version 1.
DT   18-SEP-2019, entry version 30.
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: Outer capsid protein VP4: Spike-forming protein that
CC       mediates virion attachment to the host epithelial cell receptors
CC       and plays a major role in cell penetration, determination of host
CC       range restriction and virulence. Rotavirus attachment and entry
CC       into the host cell probably involves multiple sequential contacts
CC       between the outer capsid proteins VP4 and VP7, and the cell
CC       receptors. It is subsequently lost, together with VP7, following
CC       virus entry into the host cell. Following entry into the host
CC       cell, low intracellular or intravesicular Ca(2+) concentration
CC       probably causes the calcium-stabilized VP7 trimers to dissociate
CC       from the virion. This step is probably necessary for the membrane-
CC       disrupting entry step and the release of VP4, which is locked onto
CC       the virion by VP7. {ECO:0000256|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
CC       mediates release of viral particles from endosomal compartments
CC       into the cytoplasm. During entry, the part of VP5* that protrudes
CC       from the virus folds back on itself and reorganizes from a local
CC       dimer to a trimer. This reorganization may be linked to membrane
CC       penetration by exposing VP5* hydrophobic region. In integrin-
CC       dependent strains, VP5* targets the integrin heterodimer
CC       ITGA2/ITGB1 for cell attachment. {ECO:0000256|SAAS:SAAS01043052}.
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
CC       rough endoplasmic reticulum {ECO:0000256|SAAS:SAAS01200666}.
CC       Virion {ECO:0000256|SAAS:SAAS01200667}.
CC   -!- SUBCELLULAR LOCATION: Outer capsid protein VP4: Virion
CC       {ECO:0000256|HAMAP-Rule:MF_04125}. Host rough endoplasmic
CC       reticulum {ECO:0000256|HAMAP-Rule:MF_04125}. Host cell membrane
CC       {ECO:0000256|HAMAP-Rule:MF_04125}. Host endoplasmic reticulum-
CC       Golgi intermediate compartment {ECO:0000256|HAMAP-Rule:MF_04125}.
CC       Note=The outer layer contains 180 copies of VP4, grouped as 60
CC       dimers. Immature double-layered particles assembled in the
CC       cytoplasm bud across the membrane of the endoplasmic reticulum,
CC       acquiring during this process a transient lipid membrane that is
CC       modified with the ER resident viral glycoproteins NSP4 and VP7;
CC       these enveloped particles also contain VP4. As the particles move
CC       towards the interior of the ER cisternae, the transient lipid
CC       membrane and the non-structural protein NSP4 are lost, while the
CC       virus surface proteins VP4 and VP7 rearrange to form the outermost
CC       virus protein layer, yielding mature infectious triple-layered
CC       particles. {ECO:0000256|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:0000256|HAMAP-
CC       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
CC       trypsin treatment of VP4. It produces two peptides, VP5* and VP8*
CC       that remain associated with the virion. Cleavage of VP4 by trypsin
CC       probably occurs in vivo in the lumen of the intestine prior to
CC       infection of enterocytes. Trypsin seems to be incorporated into
CC       the three-layered viral particles but remains inctive as long as
CC       the viral outer capsid is intact and would only be activated upon
CC       the solubilization of the latter. {ECO:0000256|HAMAP-
CC       Rule:MF_04125}.
CC   -!- SIMILARITY: Belongs to the rotavirus VP4 family.
CC       {ECO:0000256|HAMAP-Rule:MF_04125, ECO:0000256|SAAS:SAAS01200685}.
CC   -!- CAUTION: Lacks conserved residue(s) required for the propagation
CC       of 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   Complete proteome {ECO:0000313|Proteomes:UP000155231};
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,
KW   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-
KW   Rule:MF_04125, ECO:0000256|SAAS:SAAS01200663};
KW   Viral penetration via permeabilization of host membrane
KW   {ECO:0000256|HAMAP-Rule:MF_04125, ECO:0000256|SAAS:SAAS01200668};
KW   Virion {ECO:0000256|HAMAP-Rule:MF_04125,
KW   ECO:0000256|SAAS:SAAS01200664};
KW   Virus entry into host cell {ECO:0000256|HAMAP-Rule:MF_04125,
KW   ECO:0000256|SAAS:SAAS01200683}.
FT   DOMAIN      249    473       Rota_VP4_MID. {ECO:0000259|Pfam:PF17477}.
FT   DOMAIN      485    775       VP4_helical. {ECO:0000259|Pfam:PF17478}.
FT   COILED      483    510       {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
//