ID A0A024CFA7_9REOV Unreviewed; 775 AA. AC A0A024CFA7; DT 09-JUL-2014, integrated into UniProtKB/TrEMBL. DT 09-JUL-2014, sequence version 1. DT 31-JUL-2019, entry version 29. 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}. 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-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; 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 //