ID VP4_ROTRH Reviewed; 776 AA. AC P12473; P11201; Q86214; Q86215; Q91HI9; DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot. DT 24-MAR-2009, sequence version 2. DT 08-NOV-2023, entry version 132. DE RecName: Full=Outer capsid protein VP4 {ECO:0000255|HAMAP-Rule:MF_04132}; DE AltName: Full=Hemagglutinin {ECO:0000255|HAMAP-Rule:MF_04132}; DE Contains: DE RecName: Full=Outer capsid protein VP8* {ECO:0000255|HAMAP-Rule:MF_04132}; DE Contains: DE RecName: Full=Outer capsid protein VP5* {ECO:0000255|HAMAP-Rule:MF_04132}; OS Rotavirus A (strain RVA/Monkey/United States/RRV/1975/G3P5B[3]) (RV-A). OC Viruses; Riboviria; Orthornavirae; Duplornaviricota; Resentoviricetes; OC Reovirales; Sedoreoviridae; Rotavirus; Rotavirus A. OX NCBI_TaxID=444185; OH NCBI_TaxID=9544; Macaca mulatta (Rhesus macaque). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=2829198; DOI=10.1073/pnas.85.3.645; RA Mackow E.R., Shaw R.D., Matsui S.M., Vo P.T., Dang M.-N., Greenberg H.G.; RT "The rhesus rotavirus gene encoding protein VP3: location of amino acids RT involved in homologous and heterologous rotavirus neutralization and RT identification of a putative fusion region."; RL Proc. Natl. Acad. Sci. U.S.A. 85:645-649(1988). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=11462006; DOI=10.1128/jvi.75.16.7339-7350.2001; RA Dormitzer P.R., Greenberg H.B., Harrison S.C.; RT "Proteolysis of monomeric recombinant rotavirus VP4 yields an oligomeric RT VP5* core."; RL J. Virol. 75:7339-7350(2001). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-281. RC STRAIN=Isolate MMU-18006; RX PubMed=3018754; DOI=10.1073/pnas.83.18.7039; RA Gorziglia M., Hoshino Y., Buckler-White A., Blumentals I., Glass R., RA Flores J., Kapikian A.Z., Chanock R.M.; RT "Conservation of amino acid sequence of VP8 and cleavage region of 84-kDa RT outer capsid protein among rotaviruses recovered from asymptomatic neonatal RT infection."; RL Proc. Natl. Acad. Sci. U.S.A. 83:7039-7043(1986). RN [4] RP DISULFIDE BONDS (OUTER CAPSID PROTEIN VP4). RX PubMed=8392619; DOI=10.1128/jvi.67.8.4848-4855.1993; RA Patton J.T., Hua J.J., Mansell E.A.; RT "Location of intrachain disulfide bonds in the VP5* and VP8* trypsin RT cleavage fragments of the rhesus rotavirus spike protein VP4."; RL J. Virol. 67:4848-4855(1993). RN [5] RP PROTEOLYTIC CLEAVAGE (OUTER CAPSID PROTEIN VP4). RX PubMed=8709201; DOI=10.1128/jvi.70.9.5832-5839.1996; RA Arias C.F., Romero P., Alvarez V., Lopez S.; RT "Trypsin activation pathway of rotavirus infectivity."; RL J. Virol. 70:5832-5839(1996). RN [6] RP PROTEOLYTIC CLEAVAGE (OUTER CAPSID PROTEIN VP4), AND MUTAGENESIS OF RP ARG-231; ARG-241 AND ARG-247. RX PubMed=9573313; DOI=10.1128/jvi.72.6.5323-5327.1998; RA Gilbert J.M., Greenberg H.B.; RT "Cleavage of rhesus rotavirus VP4 after arginine 247 is essential for RT rotavirus-like particle-induced fusion from without."; RL J. Virol. 72:5323-5327(1998). RN [7] RP INTERACTION WITH INTEGRIN HETERODIMER ITGA2/ITGB1 (OUTER CAPSID PROTEIN RP VP5*). RC STRAIN=nar3, and RRV; RX PubMed=11112480; DOI=10.1006/viro.2000.0660; RA Zarate S., Espinosa R., Romero P., Guerrero C.A., Arias C.F., Lopez S.; RT "Integrin alpha2beta1 mediates the cell attachment of the rotavirus RT neuraminidase-resistant variant nar3."; RL Virology 278:50-54(2000). RN [8] RP SUBCELLULAR LOCATION (OUTER CAPSID PROTEIN VP4). RX PubMed=10708448; DOI=10.1128/jvi.74.7.3313-3320.2000; RA Nejmeddine M., Trugnan G., Sapin C., Kohli E., Svensson L., Lopez S., RA Cohen J.; RT "Rotavirus spike protein VP4 is present at the plasma membrane and is RT associated with microtubules in infected cells."; RL J. Virol. 74:3313-3320(2000). RN [9] RP SIALIC ACID DEPENDENCY. RX PubMed=11907248; DOI=10.1128/jvi.76.8.4087-4095.2002; RA Ciarlet M., Ludert J.E., Iturriza-Gomara M., Liprandi F., Gray J.J., RA Desselberger U., Estes M.K.; RT "Initial interaction of rotavirus strains with N-acetylneuraminic (sialic) RT acid residues on the cell surface correlates with VP4 genotype, not species RT of origin."; RL J. Virol. 76:4087-4095(2002). RN [10] RP INTERACTION WITH HSPA8/HSP70 (OUTER CAPSID PROTEIN VP5*). RX PubMed=12805424; DOI=10.1128/jvi.77.13.7254-7260.2003; RA Zarate S., Cuadras M.A., Espinosa R., Romero P., Juarez K.O., RA Camacho-Nuez M., Arias C.F., Lopez S.; RT "Interaction of rotaviruses with Hsc70 during cell entry is mediated by RT VP5."; RL J. Virol. 77:7254-7260(2003). RN [11] RP REVIEW. RX PubMed=15165605; DOI=10.1016/j.tim.2004.04.003; RA Lopez S., Arias C.F.; RT "Multistep entry of rotavirus into cells: a Versaillesque dance."; RL Trends Microbiol. 12:271-278(2004). RN [12] RP INTERACTION WITH HUMAN INTEGRIN HETERODIMER ITGA4/ITGB1 (OUTER CAPSID RP PROTEIN VP5*), AND INTERACTION WITH HUMAN INTEGRIN HETERODIMER ITGA4/ITGB7 RP (OUTER CAPSID PROTEIN VP5*). RX PubMed=16298987; DOI=10.1099/vir.0.81102-0; RA Graham K.L., Fleming F.E., Halasz P., Hewish M.J., Nagesha H.S., RA Holmes I.H., Takada Y., Coulson B.S.; RT "Rotaviruses interact with alpha4beta7 and alpha4beta1 integrins by binding RT the same integrin domains as natural ligands."; RL J. Gen. Virol. 86:3397-3408(2005). RN [13] RP FUNCTION (OUTER CAPSID PROTEIN VP4), AND SUBCELLULAR LOCATION (OUTER CAPSID RP PROTEIN VP4). RX PubMed=16571810; DOI=10.1128/jvi.80.8.3935-3946.2006; RA Cuadras M.A., Bordier B.B., Zambrano J.L., Ludert J.E., Greenberg H.B.; RT "Dissecting rotavirus particle-raft interaction with small interfering RT RNAs: insights into rotavirus transit through the secretory pathway."; RL J. Virol. 80:3935-3946(2006). RN [14] RP REVIEW. RX PubMed=16575520; DOI=10.1007/s10719-006-5435-y; RA Isa P., Arias C.F., Lopez S.; RT "Role of sialic acids in rotavirus infection."; RL Glycoconj. J. 23:27-37(2006). RN [15] RP INTERACTION WITH SIMIAN INTEGRIN HETERODIMER ITGA2/ITGB1 (OUTER CAPSID RP PROTEIN VP5*). RX PubMed=16603530; DOI=10.1099/vir.0.81580-0; RA Graham K.L., Takada Y., Coulson B.S.; RT "Rotavirus spike protein VP5* binds alpha2beta1 integrin on the cell RT surface and competes with virus for cell binding and infectivity."; RL J. Gen. Virol. 87:1275-1283(2006). RN [16] RP FUNCTION (OUTER CAPSID PROTEIN VP5*), MUTAGENESIS OF LEU-287; LEU-333; RP VAL-391 AND TRP-394, AND FUNCTION (OUTER CAPSID PROTEIN VP8*). RX PubMed=20375171; DOI=10.1128/jvi.02461-09; RA Kim I.S., Trask S.D., Babyonyshev M., Dormitzer P.R., Harrison S.C.; RT "Effect of mutations in VP5 hydrophobic loops on rotavirus cell entry."; RL J. Virol. 84:6200-6207(2010). RN [17] RP FUNCTION (OUTER CAPSID PROTEIN VP4). RX PubMed=25211455; DOI=10.1371/journal.ppat.1004355; RA Abdelhakim A.H., Salgado E.N., Fu X., Pasham M., Nicastro D., RA Kirchhausen T., Harrison S.C.; RT "Structural correlates of rotavirus cell entry."; RL PLoS Pathog. 10:E1004355-E1004355(2014). RN [18] RP DOMAIN (OUTER CAPSID PROTEIN VP4), INTERACTION WITH VP6 (OUTER CAPSID RP PROTEIN VP4), AND INTERACTION WITH VP7 (OUTER CAPSID PROTEIN VP4). RX PubMed=21157433; DOI=10.1038/emboj.2010.322; RA Settembre E.C., Chen J.Z., Dormitzer P.R., Grigorieff N., Harrison S.C.; RT "Atomic model of an infectious rotavirus particle."; RL EMBO J. 30:408-416(2011). RN [19] RP FUNCTION (OUTER CAPSID PROTEIN VP8*). RX PubMed=29136651; DOI=10.1371/journal.ppat.1006707; RA Liu Y., Xu S., Woodruff A.L., Xia M., Tan M., Kennedy M.A., Jiang X.; RT "Structural basis of glycan specificity of P[19] VP8*: Implications for RT rotavirus zoonosis and evolution."; RL PLoS Pathog. 13:E1006707-E1006707(2017). RN [20] RP SUBCELLULAR LOCATION (OUTER CAPSID PROTEIN VP4). RX PubMed=29263265; DOI=10.1128/jvi.02076-17; RA Trejo-Cerro O., Eichwald C., Schraner E.M., Silva-Ayala D., Lopez S., RA Arias C.F.; RT "Actin-dependent non-lytic rotavirus exit and infectious virus RT morphogenetic pathway in non-polarized cells."; RL J. Virol. 0:0-0(2017). RN [21] RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 62-224, AND STRUCTURE BY NMR OF RP 46-231. RX PubMed=11867517; DOI=10.1093/emboj/21.5.885; RA Dormitzer P.R., Sun Z.Y., Wagner G., Harrison S.C.; RT "The rhesus rotavirus VP4 sialic acid binding domain has a galectin fold RT with a novel carbohydrate binding site."; RL EMBO J. 21:885-897(2002). RN [22] RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 248-525, INTERACTION WITH VP6 RP (OUTER CAPSID PROTEIN VP4), INTERACTION WITH VP7 (OUTER CAPSID PROTEIN RP VP4), SUBCELLULAR LOCATION (OUTER CAPSID PROTEIN VP5*), SUBCELLULAR RP LOCATION (OUTER CAPSID PROTEIN VP8*), AND SUBUNIT (OUTER CAPSID PROTEIN RP VP4). RX PubMed=15329727; DOI=10.1038/nature02836; RA Dormitzer P.R., Nason E.B., Prasad B.V.V., Harrison S.C.; RT "Structural rearrangements in the membrane penetration protein of a non- RT enveloped virus."; RL Nature 430:1053-1058(2004). RN [23] {ECO:0007744|PDB:2B4H, ECO:0007744|PDB:2B4I} RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 247-479, SUBUNIT (OUTER CAPSID RP PROTEIN VP5*), FUNCTION (OUTER CAPSID PROTEIN VP5*), AND SUBUNIT (OUTER RP CAPSID PROTEIN VP4). RX PubMed=16511559; DOI=10.1038/sj.emboj.7601034; RA Yoder J.D., Dormitzer P.R.; RT "Alternative intermolecular contacts underlie the rotavirus VP5* two- to RT three-fold rearrangement."; RL EMBO J. 25:1559-1568(2006). RN [24] {ECO:0007744|PDB:2P3I, ECO:0007744|PDB:2P3J, ECO:0007744|PDB:2P3K} RP X-RAY CRYSTALLOGRAPHY (1.56 ANGSTROMS) OF 64-224, MUTAGENESIS OF ARG-101 RP AND SER-190, AND SIALIC ACID DEPENDENCY. RX PubMed=18974199; DOI=10.1093/glycob/cwn119; RA Kraschnefski M.J., Bugarcic A., Fleming F.E., Yu X., von Itzstein M., RA Coulson B.S., Blanchard H.; RT "Effects on sialic acid recognition of amino acid mutations in the RT carbohydrate-binding cleft of the rotavirus spike protein."; RL Glycobiology 19:194-200(2009). RN [25] {ECO:0007744|PDB:3TB0} RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 64-224. RX PubMed=23035213; DOI=10.1128/jvi.06975-11; RA Yu X., Dang V.T., Fleming F.E., von Itzstein M., Coulson B.S., RA Blanchard H.; RT "Structural basis of rotavirus strain preference toward N-acetyl- or N- RT glycolylneuraminic acid-containing receptors."; RL J. Virol. 86:13456-13466(2012). CC -!- FUNCTION: [Outer capsid protein VP4]: Spike-forming protein that CC mediates virion attachment to the host epithelial cell receptors and CC plays a major role in cell penetration, determination of host range CC restriction and virulence (PubMed:25211455). Rotavirus attachment and CC entry into the host cell probably involves multiple sequential contacts CC between the outer capsid proteins VP4 and VP7, and the cell receptors CC (PubMed:15165605). It is subsequently lost, together with VP7, CC following virus entry into the host cell (PubMed:15165605). 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 (PubMed:25211455). This step is probably CC necessary for the membrane-disrupting entry step and the release of CC VP4, which is locked onto the virion by VP7 (PubMed:25211455). During CC the virus exit from the host cell, VP4 seems to be required to target CC the newly formed virions to the host cell lipid rafts CC (PubMed:16571810). {ECO:0000269|PubMed:16571810, CC ECO:0000269|PubMed:25211455, ECO:0000303|PubMed:15165605}. CC -!- FUNCTION: [Outer capsid protein VP5*]: Forms the spike 'foot' and CC 'body' and acts as a membrane permeabilization protein that mediates CC release of viral particles from endosomal compartments into the CC cytoplasm. During entry, the part of VP5* that protrudes from the virus CC folds back on itself and reorganizes from a local dimer to a trimer. CC This reorganization may be linked to membrane penetration by exposing CC VP5* hydrophobic region. In integrin-dependent strains, VP5* targets CC the integrin heterodimer ITGA2/ITGB1 for cell attachment. CC {ECO:0000255|HAMAP-Rule:MF_04132, ECO:0000269|PubMed:16511559, CC ECO:0000269|PubMed:20375171}. 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 contact CC (PubMed:20375171). In some other strains, VP8* mediates the attachment CC to histo-blood group antigens (HBGAs) for viral entry CC (PubMed:29136651). {ECO:0000255|HAMAP-Rule:MF_04132, CC ECO:0000269|PubMed:20375171, ECO:0000269|PubMed:29136651}. 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 (PubMed:15329727). Interacts with CC VP6 (PubMed:15329727, PubMed:21157433). Interacts with VP7 CC (PubMed:15329727, PubMed:21157433). {ECO:0000269|PubMed:15329727, CC ECO:0000305}. CC -!- SUBUNIT: [Outer capsid protein VP5*]: Homotrimer. The trimer is coiled- CC coil stabilized by its C-terminus, however, its N-terminus, known as CC antigen domain or 'body', seems to be flexible allowing it to self- CC associate either as a dimer or a trimer (PubMed:16511559). Interacts CC with host ITGA2 (via ITAG2 I-domain); this interaction occurs when CC ITGA2 is part of the integrin heterodimer ITGA2/ITGB1 (PubMed:11112480, CC PubMed:16603530). Interacts with host integrin heterodimer ITGA4/ITGB1 CC and ITGA4/ITGB7 (PubMed:16298987). Interacts with host HSPA8/HSP70 CC (PubMed:12805424). {ECO:0000269|PubMed:11112480, CC ECO:0000269|PubMed:12805424, ECO:0000269|PubMed:16298987, CC ECO:0000269|PubMed:16511559, ECO:0000269|PubMed:16603530, ECO:0000305}. CC -!- SUBCELLULAR LOCATION: [Outer capsid protein VP4]: Virion CC {ECO:0000255|HAMAP-Rule:MF_04132, ECO:0000269|PubMed:15329727, CC ECO:0000269|PubMed:29263265}. Host rough endoplasmic reticulum CC {ECO:0000255|HAMAP-Rule:MF_04132}. Host cell membrane CC {ECO:0000255|HAMAP-Rule:MF_04132, ECO:0000269|PubMed:29263265}. Host CC cytoplasm, host cytoskeleton {ECO:0000255|HAMAP-Rule:MF_04132}. Host CC endoplasmic reticulum-Golgi intermediate compartment CC {ECO:0000255|HAMAP-Rule:MF_04132, ECO:0000269|PubMed:16571810}. CC Note=The outer layer contains 180 copies of VP4, grouped as 60 dimers CC (By similarity). 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; these CC enveloped particles also contain VP4. As the particles move towards the CC interior of the ER cisternae, the transient lipid membrane and the non- CC structural protein NSP4 are lost, while the virus surface proteins VP4 CC and VP7 rearrange to form the outermost virus protein layer, yielding CC mature infectious triple-layered particles. VP4 also seems to associate CC with lipid rafts of the host cell membrane probably for the exit of the CC virus from the infected cell by an alternate pathway (PubMed:10708448, CC PubMed:16571810, PubMed:29263265). {ECO:0000255|HAMAP-Rule:MF_04132, CC ECO:0000269|PubMed:10708448, ECO:0000269|PubMed:16571810, CC ECO:0000269|PubMed:29263265}. CC -!- SUBCELLULAR LOCATION: [Outer capsid protein VP8*]: Virion CC {ECO:0000255|HAMAP-Rule:MF_04132, ECO:0000269|PubMed:15329727, CC ECO:0000269|PubMed:29263265}. Note=Outer capsid protein. CC {ECO:0000255|HAMAP-Rule:MF_04132, ECO:0000269|PubMed:15329727}. CC -!- SUBCELLULAR LOCATION: [Outer capsid protein VP5*]: Virion CC {ECO:0000255|HAMAP-Rule:MF_04132, ECO:0000269|PubMed:15329727, CC ECO:0000269|PubMed:29263265}. Note=Outer capsid protein. CC {ECO:0000255|HAMAP-Rule:MF_04132, ECO:0000269|PubMed:15329727}. 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-Rule:MF_04132, CC ECO:0000269|PubMed:21157433}. 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 trypsin CC treatment of VP4. It produces two peptides, VP5* and VP8* that remain CC associated with the virion (PubMed:8709201, PubMed:9573313). Cleavage CC of VP4 by trypsin occurs in vivo in the lumen of the intestine prior to CC infection of enterocytes (By similarity). {ECO:0000255|HAMAP- CC Rule:MF_04132, ECO:0000269|PubMed:8709201, ECO:0000269|PubMed:9573313}. CC -!- MISCELLANEOUS: In group A rotaviruses, VP4 defines the P serotype. CC {ECO:0000255|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:0000255|HAMAP- CC Rule:MF_04132, ECO:0000269|PubMed:15165605}. CC -!- MISCELLANEOUS: This strain probably uses sialic acid to attach to the CC host cell. {ECO:0000255|HAMAP-Rule:MF_04132, CC ECO:0000269|PubMed:11907248, ECO:0000269|PubMed:18974199, CC ECO:0000303|PubMed:16575520}. CC -!- SIMILARITY: Belongs to the rotavirus VP4 family. {ECO:0000255|HAMAP- CC 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; M18736; AAA47345.1; -; Genomic_RNA. DR EMBL; AY033150; AAK52093.1; -; mRNA. DR PIR; A31078; VPXRRH. DR PIR; I25904; VPXRRR. DR PDB; 1KQR; X-ray; 1.40 A; A=62-224. DR PDB; 1KRI; NMR; -; A=46-231. DR PDB; 1SLQ; X-ray; 3.20 A; A/B/C/D/E/F=248-525. DR PDB; 2B4H; X-ray; 1.60 A; A/B=248-479. DR PDB; 2B4I; X-ray; 2.00 A; A/B/C=248-479. DR PDB; 2P3I; X-ray; 1.75 A; A=64-224. DR PDB; 2P3J; X-ray; 1.90 A; A=64-224. DR PDB; 2P3K; X-ray; 1.56 A; A=64-224. DR PDB; 3TB0; X-ray; 2.00 A; A=64-224. DR PDBsum; 1KQR; -. DR PDBsum; 1KRI; -. DR PDBsum; 1SLQ; -. DR PDBsum; 2B4H; -. DR PDBsum; 2B4I; -. DR PDBsum; 2P3I; -. DR PDBsum; 2P3J; -. DR PDBsum; 2P3K; -. DR PDBsum; 3TB0; -. DR BMRB; P12473; -. DR SMR; P12473; -. DR TCDB; 1.G.19.1.1; the rotavirus pore-forming membrane fusion complex (rotavirus mfc) family. DR UniLectin; P12473; -. DR EvolutionaryTrace; P12473; -. 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 Gene3D; 1.20.5.170; -; 1. DR Gene3D; 2.60.120.200; -; 1. 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; IPR000416; VP4_concanavalin-like. DR InterPro; IPR035329; VP4_helical. DR Pfam; PF17477; Rota_VP4_MID; 1. DR Pfam; PF00426; VP4_haemagglut; 1. DR Pfam; PF17478; VP4_helical; 1. DR SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 1. DR SUPFAM; SSF111379; VP4 membrane interaction domain; 1. PE 1: Evidence at protein level; KW 3D-structure; Capsid protein; Coiled coil; Disulfide bond; Hemagglutinin; KW Host cell membrane; Host cytoplasm; Host cytoskeleton; 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..776 FT /note="Outer capsid protein VP4" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132" FT /id="PRO_0000041108" FT CHAIN 1..231 FT /note="Outer capsid protein VP8*" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132" FT /id="PRO_0000041109" FT CHAIN 248..776 FT /note="Outer capsid protein VP5*" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132" FT /id="PRO_0000041110" FT REGION 65..224 FT /note="Spike head" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132, FT ECO:0000269|PubMed:21157433" FT REGION 248..479 FT /note="Spike body and stalk (antigen domain)" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132, FT ECO:0000269|PubMed:21157433" FT REGION 389..409 FT /note="Hydrophobic; possible role in virus entry into host FT cell" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132, FT ECO:0000269|PubMed:20375171" FT REGION 510..776 FT /note="Spike foot" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132, FT ECO:0000269|PubMed:21157433" FT COILED 484..511 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132, FT ECO:0000269|PubMed:21157433" FT MOTIF 308..310 FT /note="DGE motif; interaction with ITGA2/ITGB1 heterodimer" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132, FT ECO:0000269|PubMed:11112480" FT MOTIF 448..450 FT /note="YGL motif; interaction with ITGA4" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132, FT ECO:0000269|PubMed:16298987" FT MOTIF 644..646 FT /note="KID motif; interaction with HSPA8" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132, FT ECO:0000269|PubMed:12805424" FT SITE 101 FT /note="Binding to sialic acid" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132, FT ECO:0000269|PubMed:18974199" FT SITE 190 FT /note="Binding to sialic acid" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132, FT ECO:0000269|PubMed:18974199" FT SITE 231..232 FT /note="Cleavage" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132, FT ECO:0000269|PubMed:8709201" FT SITE 241..242 FT /note="Cleavage" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132, FT ECO:0000269|PubMed:8709201" FT SITE 247..248 FT /note="Cleavage; associated with enhancement of FT infectivity" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132, FT ECO:0000269|PubMed:8709201, ECO:0000269|PubMed:9573313" FT DISULFID 203..216 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132, FT ECO:0000269|PubMed:8392619" FT DISULFID 318..380 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04132, FT ECO:0000269|PubMed:8392619" FT VARIANT 109..110 FT /note="EP -> VA (in strain: Isolate MMU-18006)" FT VARIANT 146 FT /note="T -> S (in strain: Isolate MMU-18006)" FT VARIANT 166 FT /note="A -> G (in strain: Isolate MMU-18006)" FT VARIANT 235..240 FT /note="PLALSA -> LALSAS (in strain: Isolate MMU-18006)" FT VARIANT 244..245 FT /note="IS -> TY (in strain: Isolate MMU-18006)" FT MUTAGEN 101 FT /note="R->A: Reduced ability to bind sialic acid binding." FT /evidence="ECO:0000269|PubMed:18974199" FT MUTAGEN 190 FT /note="S->A: Reduced ability to bind sialic acid." FT /evidence="ECO:0000269|PubMed:18974199" FT MUTAGEN 231 FT /note="R->H: Complete loss of trypsin activation of VP4, FT resulting in a blockage to viral entry." FT /evidence="ECO:0000269|PubMed:9573313" FT MUTAGEN 241 FT /note="R->H: Complete loss of trypsin activation of VP4, FT resulting in a blockage to viral entry." FT /evidence="ECO:0000269|PubMed:9573313" FT MUTAGEN 247 FT /note="R->H: Complete loss of trypsin activation of VP4, FT resulting in a blockage to viral entry and inhability to FT induce polykaryon formation. This cleavage is required to FT promote viral entry." FT /evidence="ECO:0000269|PubMed:9573313" FT MUTAGEN 287 FT /note="L->D: About 50% loss of association with liposomes." FT /evidence="ECO:0000269|PubMed:20375171" FT MUTAGEN 333 FT /note="L->D: Slight loss of infectivity. About 50% loss of FT association with liposomes." FT /evidence="ECO:0000269|PubMed:20375171" FT MUTAGEN 391 FT /note="V->D: Drastic loss of infectivity by blocking the FT host membrane permeabilization after virus internalization. FT Almost complete loss of association with liposomes." FT /evidence="ECO:0000269|PubMed:20375171" FT MUTAGEN 394 FT /note="W->Q: Slight loss of infectivity. No effect on the FT association with liposomes." FT /evidence="ECO:0000269|PubMed:20375171" FT CONFLICT 73 FT /note="S -> T (in Ref. 2; AAK52093)" FT /evidence="ECO:0000305" FT CONFLICT 132 FT /note="N -> Y (in Ref. 1; AAA47345)" FT /evidence="ECO:0000305" FT CONFLICT 311 FT /note="D -> E (in Ref. 2; AAK52093)" FT /evidence="ECO:0000305" FT CONFLICT 338 FT /note="I -> V (in Ref. 2; AAK52093)" FT /evidence="ECO:0000305" FT CONFLICT 421 FT /note="F -> L (in Ref. 2; AAK52093)" FT /evidence="ECO:0000305" FT CONFLICT 445..446 FT /note="GG -> SR (in Ref. 2; AAK52093)" FT /evidence="ECO:0000305" FT CONFLICT 454 FT /note="Y -> N (in Ref. 2; AAK52093)" FT /evidence="ECO:0000305" FT CONFLICT 468 FT /note="L -> F (in Ref. 2; AAK52093)" FT /evidence="ECO:0000305" FT CONFLICT 519 FT /note="Y -> D (in Ref. 2; AAK52093)" FT /evidence="ECO:0000305" FT CONFLICT 690 FT /note="Y -> F (in Ref. 2; AAK52093)" FT /evidence="ECO:0000305" FT STRAND 66..69 FT /evidence="ECO:0007829|PDB:1KQR" FT STRAND 71..74 FT /evidence="ECO:0007829|PDB:1KQR" FT STRAND 80..84 FT /evidence="ECO:0007829|PDB:1KQR" FT STRAND 88..96 FT /evidence="ECO:0007829|PDB:1KQR" FT STRAND 98..100 FT /evidence="ECO:0007829|PDB:1KQR" FT STRAND 102..108 FT /evidence="ECO:0007829|PDB:1KQR" FT STRAND 110..121 FT /evidence="ECO:0007829|PDB:1KQR" FT STRAND 124..132 FT /evidence="ECO:0007829|PDB:1KQR" FT STRAND 135..147 FT /evidence="ECO:0007829|PDB:1KQR" FT STRAND 153..162 FT /evidence="ECO:0007829|PDB:1KQR" FT STRAND 165..170 FT /evidence="ECO:0007829|PDB:1KQR" FT STRAND 173..180 FT /evidence="ECO:0007829|PDB:1KQR" FT STRAND 185..190 FT /evidence="ECO:0007829|PDB:1KQR" FT HELIX 194..196 FT /evidence="ECO:0007829|PDB:1KQR" FT STRAND 198..203 FT /evidence="ECO:0007829|PDB:1KQR" FT STRAND 205..209 FT /evidence="ECO:0007829|PDB:1KQR" FT HELIX 210..212 FT /evidence="ECO:0007829|PDB:1KQR" FT HELIX 213..222 FT /evidence="ECO:0007829|PDB:1KQR" FT STRAND 249..258 FT /evidence="ECO:0007829|PDB:2B4I" FT STRAND 260..275 FT /evidence="ECO:0007829|PDB:2B4I" FT STRAND 278..283 FT /evidence="ECO:0007829|PDB:2B4I" FT STRAND 290..297 FT /evidence="ECO:0007829|PDB:2B4I" FT STRAND 299..307 FT /evidence="ECO:0007829|PDB:2B4I" FT STRAND 310..322 FT /evidence="ECO:0007829|PDB:2B4I" FT STRAND 324..329 FT /evidence="ECO:0007829|PDB:2B4I" FT STRAND 338..345 FT /evidence="ECO:0007829|PDB:2B4I" FT STRAND 350..359 FT /evidence="ECO:0007829|PDB:2B4I" FT HELIX 360..362 FT /evidence="ECO:0007829|PDB:2B4I" FT STRAND 367..375 FT /evidence="ECO:0007829|PDB:2B4I" FT STRAND 378..381 FT /evidence="ECO:0007829|PDB:2B4I" FT STRAND 384..386 FT /evidence="ECO:0007829|PDB:1SLQ" FT STRAND 390..392 FT /evidence="ECO:0007829|PDB:2B4I" FT STRAND 396..399 FT /evidence="ECO:0007829|PDB:2B4I" FT STRAND 401..415 FT /evidence="ECO:0007829|PDB:2B4I" FT STRAND 420..432 FT /evidence="ECO:0007829|PDB:2B4I" FT STRAND 437..439 FT /evidence="ECO:0007829|PDB:2B4I" FT STRAND 449..454 FT /evidence="ECO:0007829|PDB:2B4I" FT TURN 455..458 FT /evidence="ECO:0007829|PDB:2B4I" FT STRAND 462..475 FT /evidence="ECO:0007829|PDB:2B4I" FT HELIX 492..512 FT /evidence="ECO:0007829|PDB:1SLQ" FT TURN 513..519 FT /evidence="ECO:0007829|PDB:1SLQ" SQ SEQUENCE 776 AA; 86554 MW; C012EB9E3816A3F9 CRC64; MASLIYRQLL TNSYTVDLSD EIQEIGSTKT QNVTINLGPF AQTGYAPVNW GPGETNDSTT VEPVLDGPYQ PTSFNPPVDY WMLLAPTAAG VVVEGTNNTD RWLATILVEP NVTSETRSYT LFGTQEQITI ANASQTQWKF IDVVKTTQNG SYSQYGPLQS TPKLYAVMKH NGKIYTYNGE TPNVTTKYYS TTNYDSVNMT AFCDFYIIPR EEESTCTEYI NNGLPPIQNT RNIVPLALSA RNIISHRAQA NEDIVVSKTS LWKEMQYNRD ITIRFKFASS IVKSGGLGYK WSEISFKPAN YQYTYTRDGE DVTAHTTCSV NGMNDFNFNG GSLPTDFIIS RYEVIKENSY VYVDYWDDSQ AFRNMVYVRS LAANLNSVIC TGGDYSFALP VGQWPVMTGG AVSLHSAGVT LSTQFTDFVS FNSLRFRFRL TVEEPSFSIT RTRVGGLYGL PAAYPNNGKE YYEVAGRLSL ISLVPSNDDY QTPITNSVTV RQDLERQLGE LREEFNALSQ EIAMSQLIYL ALLPLDMFSM FSGIKSTIDA AKSMATSVMK KFKKSGLANS VSTLTDSLSD AASSISRGAS IRSVGSSASA WTDVSTQITD VSSSVSSIST QTSTISRRLR LKEMATQTEG MNFDDISAAV LKTKIDRSTQ ISPNTLPDIV TEASEKFIPN RAYRVINNDE VFEAGTDGRY FAYRVETFDE IPFDVQKFAD LVTDSPVISA IIDFKTLKNL NDNYGISRQQ AFNLLRSDPR VLREFINQDN PIIRNRIEQL IMQCRL //