ID A0A024CFA7_9REOV Unreviewed; 775 AA. AC A0A024CFA7; DT 09-JUL-2014, integrated into UniProtKB/TrEMBL. DT 09-JUL-2014, sequence version 1. DT 07-APR-2021, entry version 37. DE RecName: Full=Outer capsid protein VP4 {ECO:0000256|HAMAP-Rule:MF_04132}; DE AltName: Full=Hemagglutinin {ECO:0000256|HAMAP-Rule:MF_04132}; DE Contains: DE RecName: Full=Outer capsid protein VP8* {ECO:0000256|HAMAP-Rule:MF_04132}; DE Contains: DE RecName: Full=Outer capsid protein VP5* {ECO:0000256|HAMAP-Rule:MF_04132}; GN Name=VP4 {ECO:0000313|EMBL:AHZ33086.1}; GN ORFNames=L312_46656gpVP4 {ECO:0000313|EMBL:AHZ33086.1}; OS Rotavirus A. OC Viruses; Riboviria; Orthornavirae; Duplornaviricota; Resentoviricetes; OC Reovirales; 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 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. 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:0000256|HAMAP-Rule:MF_04132}. CC -!- FUNCTION: Outer capsid protein VP5*: Forms the spike 'foot' and 'body' CC and acts as a membrane permeabilization protein that mediates release CC of viral particles from endosomal compartments into the cytoplasm. CC During entry, the part of VP5* that protrudes from the virus folds back CC on itself and reorganizes from a local dimer to a trimer. This CC reorganization may be linked to membrane penetration by exposing VP5* CC hydrophobic region. In integrin-dependent strains, VP5* targets the CC integrin heterodimer ITGA2/ITGB1 for cell attachment. CC {ECO:0000256|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:0000256|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. Outer capsid protein VP4: CC Interacts with VP6. Outer capsid protein VP4: Interacts with VP7. Outer CC capsid protein VP5*: Homotrimer. The trimer is coiled-coil stabilized CC by its C-terminus, however, its N-terminus, known as antigen domain or CC 'body', seems to be flexible allowing it to self-associate either as a CC dimer or a trimer. {ECO:0000256|HAMAP-Rule:MF_04132}. CC -!- SUBCELLULAR LOCATION: [Outer capsid protein VP5*]: Virion CC {ECO:0000256|HAMAP-Rule:MF_04132}. Note=Outer capsid protein. CC {ECO:0000256|HAMAP-Rule:MF_04132}. CC -!- SUBCELLULAR LOCATION: [Outer capsid protein VP8*]: Virion CC {ECO:0000256|HAMAP-Rule:MF_04132}. Note=Outer capsid protein. CC {ECO:0000256|HAMAP-Rule:MF_04132}. CC -!- SUBCELLULAR LOCATION: [Outer capsid protein VP4]: Virion CC {ECO:0000256|HAMAP-Rule:MF_04132}. Host rough endoplasmic reticulum CC {ECO:0000256|HAMAP-Rule:MF_04132}. Host cell membrane CC {ECO:0000256|HAMAP-Rule:MF_04132}. Host cytoplasm, host cytoskeleton CC {ECO:0000256|HAMAP-Rule:MF_04132}. Host endoplasmic reticulum-Golgi CC intermediate compartment {ECO:0000256|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:0000256|HAMAP-Rule:MF_04132}. 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_04132}. 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 inactive 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_04132}. CC -!- MISCELLANEOUS: In group A rotaviruses, VP4 defines the P serotype. CC {ECO:0000256|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:0000256|HAMAP- CC Rule:MF_04132}. CC -!- SIMILARITY: Belongs to the rotavirus VP4 family. {ECO:0000256|HAMAP- CC Rule:MF_04132}. CC -!- CAUTION: Lacks conserved residue(s) required for the propagation of CC feature annotation. {ECO:0000256|HAMAP-Rule:MF_04132}. 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; 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-KW. 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 {ECO:0000256|ARBA:ARBA00022561, ECO:0000256|HAMAP- KW Rule:MF_04132}; KW Coiled coil {ECO:0000256|ARBA:ARBA00023054, ECO:0000256|HAMAP- KW Rule:MF_04132}; Disulfide bond {ECO:0000256|HAMAP-Rule:MF_04132}; KW Hemagglutinin {ECO:0000256|ARBA:ARBA00022546, ECO:0000256|HAMAP- KW Rule:MF_04132}; KW Host cell membrane {ECO:0000256|ARBA:ARBA00022511, ECO:0000256|HAMAP- KW Rule:MF_04132}; KW Host cytoplasm {ECO:0000256|ARBA:ARBA00023200, ECO:0000256|HAMAP- KW Rule:MF_04132}; KW Host cytoskeleton {ECO:0000256|ARBA:ARBA00023111, ECO:0000256|HAMAP- KW Rule:MF_04132}; KW Host endoplasmic reticulum {ECO:0000256|ARBA:ARBA00023184, KW ECO:0000256|HAMAP-Rule:MF_04132}; KW Host membrane {ECO:0000256|ARBA:ARBA00022870, ECO:0000256|HAMAP- KW Rule:MF_04132}; KW Host-virus interaction {ECO:0000256|ARBA:ARBA00022581, ECO:0000256|HAMAP- KW Rule:MF_04132}; KW Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|HAMAP-Rule:MF_04132}; KW Outer capsid protein {ECO:0000256|ARBA:ARBA00022770, ECO:0000256|HAMAP- KW Rule:MF_04132}; KW Viral attachment to host cell {ECO:0000256|ARBA:ARBA00022804, KW ECO:0000256|HAMAP-Rule:MF_04132}; KW Viral penetration into host cytoplasm {ECO:0000256|ARBA:ARBA00022595, KW ECO:0000256|HAMAP-Rule:MF_04132}; KW Viral penetration via permeabilization of host membrane KW {ECO:0000256|ARBA:ARBA00022648, ECO:0000256|HAMAP-Rule:MF_04132}; KW Virion {ECO:0000256|ARBA:ARBA00022844, ECO:0000256|HAMAP-Rule:MF_04132}; KW Virus entry into host cell {ECO:0000256|ARBA:ARBA00023296, KW ECO:0000256|HAMAP-Rule:MF_04132}. FT CHAIN 1..775 FT /note="Outer capsid protein VP4" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04132" FT /id="PRO_5023354187" FT CHAIN 1..230 FT /note="Outer capsid protein VP8*" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04132" FT /id="PRO_5029064683" FT CHAIN 247..775 FT /note="Outer capsid protein VP5*" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04132" FT /id="PRO_5029064684" 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 REGION 51..78 FT /note="Disorded; interaction with the intermediate capsid FT protein VP6" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04132" FT REGION 247..478 FT /note="Spike body and stalk (antigen domain)" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04132" FT REGION 311..325 FT /note="Disorded" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04132" FT REGION 388..408 FT /note="Hydrophobic; possible role in virus entry into host FT cell" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04132" FT REGION 509..775 FT /note="Spike foot" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04132" FT COILED 483..510 FT /evidence="ECO:0000256|HAMAP-Rule:MF_04132" FT MOTIF 307..309 FT /note="DGE motif; interaction with ITGA2/ITGB1 heterodimer" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04132" FT MOTIF 447..449 FT /note="YGL motif; interaction with ITGA4" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04132" FT MOTIF 643..645 FT /note="KID motif; interaction with HSPA8" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04132" FT SITE 230..231 FT /note="Cleavage" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04132" FT SITE 240..241 FT /note="Cleavage" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04132" FT SITE 246..247 FT /note="Cleavage; associated with enhancement of FT infectivity" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04132" FT DISULFID 317..379 FT /evidence="ECO:0000256|HAMAP-Rule:MF_04132" 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 //