ID VP4_ROTB2 Reviewed; 826 AA. AC A9Q1L0; DT 14-APR-2009, integrated into UniProtKB/Swiss-Prot. DT 05-FEB-2008, sequence version 1. DT 05-JUN-2019, entry version 43. DE RecName: Full=Outer capsid protein VP4 {ECO:0000255|HAMAP-Rule:MF_04125}; DE AltName: Full=Hemagglutinin {ECO:0000255|HAMAP-Rule:MF_04125}; DE Contains: DE RecName: Full=Outer capsid protein VP8* {ECO:0000305}; DE Contains: DE RecName: Full=Outer capsid protein VP5* {ECO:0000305}; OS Rotavirus X (isolate RVX/Human/Bangladesh/NADRV-B219/2002/GXP[X]) (RV OS ADRV-N) (Rotavirus (isolate novel adult diarrhea rotavirus-B219)). OC Viruses; Riboviria; Reoviridae; Sedoreovirinae; Rotavirus; OC unclassified Rotavirus. OX NCBI_TaxID=348136; OH NCBI_TaxID=9606; Homo sapiens (Human). RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND PUTATIVE CLEAVAGE SITES. RX PubMed=18814255; DOI=10.1002/jmv.21286; RA Nagashima S., Kobayashi N., Ishino M., Alam M.M., Ahmed M.U., RA Paul S.K., Ganesh B., Chawla-Sarkar M., Krishnan T., Naik T.N., RA Wang Y.-H.; RT "Whole genomic characterization of a human rotavirus strain B219 RT belonging to a novel group of the genus Rotavirus."; RL J. Med. Virol. 80:2023-2033(2008). 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:0000255|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. {ECO:0000305}. CC -!- FUNCTION: Outer capsid protein VP8*: Forms the head of the spikes CC and mediates the recognition of specific host cell surface CC glycans. It is the viral hemagglutinin and an important target of CC neutralizing antibodies. {ECO:0000305}. CC -!- SUBUNIT: Outer capsid protein VP4: Homotrimer. VP4 adopts a CC dimeric appearance above the capsid surface, while forming a CC trimeric base anchored inside the capsid layer. Only hints of the CC third molecule are observed above the capsid surface. It probably CC performs a series of molecular rearrangements during viral entry. CC Prior to trypsin cleavage, it is flexible. The priming trypsin CC cleavage triggers its rearrangement into rigid spikes with CC approximate two-fold symmetry of their protruding parts. After an CC unknown second triggering event, cleaved VP4 may undergo another CC rearrangement, in which two VP5* subunits fold back on themselves CC and join a third subunit to form a tightly associated trimer, CC shaped like a folded umbrella. Outer capsid protein VP4: Interacts CC with VP6. Outer capsid protein VP4: Interacts with VP7. Outer CC capsid protein VP5*: Homotrimer. The trimer is coiled-coil CC stabilized by its C-terminus, however, its N-terminus, known as CC antigen domain or "body", seems to be flexible allowing it to CC self-associate either as a dimer or a trimer. {ECO:0000305}. CC -!- SUBCELLULAR LOCATION: Outer capsid protein VP4: Virion CC {ECO:0000255|HAMAP-Rule:MF_04125}. Host rough endoplasmic CC reticulum {ECO:0000255|HAMAP-Rule:MF_04125}. Host cell membrane CC {ECO:0000255|HAMAP-Rule:MF_04125}. Host endoplasmic reticulum- CC Golgi intermediate compartment {ECO:0000255|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:0000255|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:0000255|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:0000255|HAMAP- CC Rule:MF_04125}. CC -!- SIMILARITY: Belongs to the rotavirus VP4 family. CC {ECO:0000255|HAMAP-Rule:MF_04125}. 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; EF453358; ABR32125.1; -; mRNA. DR Proteomes; UP000174021; 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:0016020; C:membrane; IEA:UniProtKB-KW. DR GO; GO:0039624; C:viral outer capsid; IEA:UniProtKB-KW. DR GO; GO:0039665; P:permeabilization of host organelle membrane involved in viral entry into host cell; IEA:UniProtKB-KW. 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-KW. DR HAMAP; MF_04125; Rota_VP4; 1. DR InterPro; IPR035330; Rota_VP4_MID. DR InterPro; IPR038017; Rota_VP4_MID_sf. DR Pfam; PF17477; Rota_VP4_MID; 1. DR SUPFAM; SSF111379; SSF111379; 1. PE 1: Evidence at protein level; KW Capsid protein; Complete proteome; Hemagglutinin; Host cell membrane; 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 1 826 Outer capsid protein VP4. FT {ECO:0000255|HAMAP-Rule:MF_04125}. FT /FTId=PRO_0000369842. FT CHAIN 1 249 Outer capsid protein VP8*. FT /FTId=PRO_0000369843. FT CHAIN 263 826 Outer capsid protein VP5*. FT /FTId=PRO_0000369844. FT COMPBIAS 260 263 Poly-Lys. FT SITE 249 250 Probable cleavage. {ECO:0000305}. FT SITE 262 263 Probable cleavage. {ECO:0000305}. SQ SEQUENCE 826 AA; 93311 MW; B8CC3EDD7D540505 CRC64; MSLRSLLITT EAVGETTQTS DHQTSFSTRT YNEINDRPSL RVEKDGEKAY CFKNLDPVRY DTRMGEYPFD YGGQSTENNQ LQFDLFTKDL MADTDIGLSD DVRDDLKRQI KEYYQQGYRA IFLIRPQNQE QQYIASYSST NLNFTSQLSV GVNLSVLNKI QENKLHIYST QPHIPSVGCE MITKIFRTDV DNENSLINYS VPVTVTISVT KATFEDTFVW NQNNDYPNMN YKDLIPAVTK NSIYHDVKRI TKIHEYINSK KKKNGVGKIG GIQIAESKDG FWKILTKNYQ IKLKFGIEGY GVMGGTFGNW LIDSGFKTVE TNYEYQRNGK TINATTVASV KPSRKCGTRS PVFGQLQFSG EMMVLSHNDI LTVFYTEREW ALSNAIYAKN FATDFKRQFE VTAQSDELLV RTNVVPHTIK NTPGKALMEY SHGGFGQIDT SDYTGMALTF RFRCVSEDLP EGYYDKDKAL TFANVGLTSF QDRQETNGTY WVYNTSTVGF GSCYPKKEFE YDINVTYTTL LPSDPEFTTG GTNYAQSVTA VLEESFINLQ NQVNEMLTRM NISDLTSGVM SVFSVATSFP QILDGISDLL KAASSAFKKV KGKVGNVAKR LRGKRYVRLF DEDISIEETP RFLDSIRSSR RPSILSNMFN DDETFTALHT LASRTNSVAS DVTYIQPIIT TRIANSTPPV IAPASSVTYA KLKDISKIIN AEIDPKSIME FNQVSNTISI LDSTKKLAQY AVDPDVIDGI LNKMVGGHAR SLFSLKVRKH LLDAVEKDAF VKYNYHDLMG KLLNDRELLD ITNNLSSQKQ FELAKEFRDL LINALA //