VP4_ROTRH
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 23-FEB-2022, entry version 129.
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; Reoviridae; Sedoreovirinae; 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; IDA:UniProtKB.
DR GO; GO:0033691; F:sialic acid binding; IDA:UniProtKB.
DR GO; GO:0039665; P:permeabilization of host organelle membrane involved in viral entry into host cell; IDA:UniProtKB.
DR GO; GO:0046813; P:receptor-mediated virion attachment to host cell; IDA:UniProtKB.
DR GO; GO:0046718; P:viral entry into host cell; IDA:UniProtKB.
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; 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; SSF111379; SSF111379; 1.
DR SUPFAM; SSF49899; SSF49899; 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
