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P11193

- VP4_ROTHW

UniProt

P11193 - VP4_ROTHW

Protein

Outer capsid protein VP4

Gene
N/A
Organism
Rotavirus A (strain Human/United States/Wa/1974 G1-P1A[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1) (RV-A)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 98 (01 Oct 2014)
      Sequence version 3 (14 Apr 2009)
      Previous versions | rss
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    Functioni

    Spike-forming protein that mediates virion attachment to the host epithelial cell receptors and plays a major role in cell penetration, determination of host range restriction and virulence. Rotavirus entry into the host cell probably involves multiple sequential contacts between the outer capsid proteins VP4 and VP7, and the cell receptors. According to the considered strain, VP4 seems to essentially target sialic acid and/or the integrin heterodimer ITGA2/ITGB1.
    Outer capsid protein VP5*: forms the spike "foot" and "body". Acts as a membrane permeabilization protein that mediates release of viral particles from endosomal compartments into the cytoplasm. In integrin-dependent strains, VP5* targets the integrin heterodimer ITGA2/ITGB1 for cell attachment.
    VP8* forms the head of the spikes. It is the viral hemagglutinin and an important target of neutralizing antibodies. In sialic acid-dependent strains, VP8* binds to host cell sialic acid, most probably a ganglioside, providing the initial contact By similarity.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei230 – 2312CleavageBy similarity
    Sitei246 – 2472CleavageBy similarity

    GO - Biological processi

    1. permeabilization of host organelle membrane involved in viral entry into host cell Source: UniProtKB-KW
    2. virion attachment to host cell Source: UniProtKB-KW

    Keywords - Molecular functioni

    Hemagglutinin

    Keywords - Biological processi

    Host-virus interaction, Viral attachment to host cell, Viral penetration into host cytoplasm, Viral penetration via permeabilization of host membrane, Virus entry into host cell

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Outer capsid protein VP4
    Alternative name(s):
    Hemagglutinin
    Cleaved into the following 2 chains:
    OrganismiRotavirus A (strain Human/United States/Wa/1974 G1-P1A[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1) (RV-A)
    Taxonomic identifieri10962 [NCBI]
    Taxonomic lineageiVirusesdsRNA virusesReoviridaeSedoreovirinaeRotavirusRotavirus A
    Virus hostiHomo sapiens (Human) [TaxID: 9606]
    ProteomesiUP000006581: Genome

    Subcellular locationi

    Chain Outer capsid protein VP4 : Virion. Host rough endoplasmic reticulum Curated
    Note: Immature double-layered particles assembled in the cytoplasm bud across the membrane of the endoplasmic reticulum, acquiring during this process a transient lipid membrane that is modified with the ER resident viral glycoproteins NSP4 and VP7; these enveloped particles also contain VP4. As the particles move towards the interior of the ER cisternae, the transient lipid membrane and the non-structural protein NSP4 are lost, while the virus surface proteins VP4 and VP7 rearrange to form the outermost virus protein layer, yielding mature infectious triple-layered particles.
    Chain Outer capsid protein VP8* : Virion
    Note: Outer capsid protein.By similarity
    Chain Outer capsid protein VP5* : Virion
    Note: Outer capsid protein.By similarity

    GO - Cellular componenti

    1. host cell rough endoplasmic reticulum Source: UniProtKB-SubCell
    2. viral outer capsid Source: UniProtKB-KW

    Keywords - Cellular componenti

    Capsid protein, Host endoplasmic reticulum, Outer capsid protein, Virion

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 775775Outer capsid protein VP4PRO_0000041090Add
    BLAST
    Chaini1 – 230230Outer capsid protein VP8*By similarityPRO_0000041091Add
    BLAST
    Chaini247 – 775529Outer capsid protein VP5*By similarityPRO_0000041092Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi32 – 321N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi56 – 561N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi97 – 971N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi129 – 1291N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi132 – 1321N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi195 – 1951N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi317 ↔ 379Sequence Analysis
    Glycosylationi324 – 3241N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi385 – 3851N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi577 – 5771N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi583 – 5831N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi589 – 5891N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi592 – 5921N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi599 – 5991N-linked (GlcNAc...); by hostSequence Analysis

    Post-translational modificationi

    Proteolytic cleavage by trypsin results in activation of VP4 functions and greatly increases infectivity. The penetration into the host cell is dependent on trypsin treatment of VP4. It produces two peptides, VP5* and VP8* that remain associated with the virion By similarity.By similarity

    Keywords - PTMi

    Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

    Interactioni

    Subunit structurei

    VP4 is a homotrimer Potential. VP4 adopts a dimeric appearance above the capsid surface, while forming a trimeric base anchored inside the capsid layer. Only hints of the third molecule are observed above the capsid surface. It probably performs a series of molecular rearrangements during viral entry. Prior to trypsin cleavage, it is flexible. The priming trypsin cleavage triggers its rearrangement into rigid spikes with approximate two-fold symmetry of their protruding parts. After an unknown second triggering event, cleaved VP4 may undergo another rearrangement, in which two VP5* subunits fold back on themselves and join a third subunit to form a tightly associated trimer, shaped like a folded umbrella. VP5* is a homotrimer Potential. The trimer is coiled-coil stabilized by its C-terminus, however, its N-terminus, known as antigen domain or "body", seems to be flexible allowing it to self-associate either as a dimer or a trimer. The two- to three-fold reorganization and fold-back of VP5* may be linked to membrane penetration, by exposing its hydrophobic region. Interacts with host ITGA2 (via ITAG2 I-domain); this interaction occurs when ITGA2 is part of the integrin heterodimer ITGA2/ITGB1. Interacts with host integrin heterodimer ITGA4/ITGB1 and ITGA4/ITGB7 By similarity.By similarityCurated

    Structurei

    Secondary structure

    1
    775
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi66 – 694
    Beta strandi71 – 744
    Beta strandi80 – 856
    Beta strandi88 – 969
    Beta strandi98 – 1003
    Beta strandi102 – 1087
    Beta strandi110 – 12112
    Beta strandi124 – 1329
    Beta strandi134 – 14613
    Beta strandi152 – 16110
    Beta strandi163 – 1697
    Beta strandi172 – 1798
    Beta strandi184 – 1896
    Beta strandi197 – 2004
    Beta strandi204 – 2085
    Helixi209 – 2113
    Helixi212 – 22110

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2DWRX-ray2.50A65-223[»]
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP11193.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni247 – 479233Antigen domainAdd
    BLAST
    Regioni307 – 3093DGE motif; interaction with ITGA2/ITGB1 heterodimerCurated
    Regioni388 – 40821Hydrophobic; possible role in virus entry into host cellSequence AnalysisAdd
    BLAST

    Coiled coil

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Coiled coili483 – 51735Sequence AnalysisAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi559 – 61557Ser-richAdd
    BLAST

    Sequence similaritiesi

    Belongs to the rotavirus VP4 family.Curated

    Keywords - Domaini

    Coiled coil

    Family and domain databases

    Gene3Di2.60.120.200. 1 hit.
    InterProiIPR008985. ConA-like_lec_gl_sf.
    IPR013320. ConA-like_subgrp.
    IPR000416. Haemagglutinin_VP4.
    [Graphical view]
    PfamiPF00426. VP4_haemagglut. 1 hit.
    [Graphical view]
    SUPFAMiSSF49899. SSF49899. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P11193-1 [UniParc]FASTAAdd to Basket

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    MASLIYRQLL TNSYSVDLHD EIEQIGSEKT QNVTINPSPF AQTRYAPVNW    50
    GHGEINDSTT VEPILDGPYQ PTTFTPPNDY WILINSNTNG VVYESTNNSD 100
    FWTAVVAIEP HVNPVDRQYT IFGESKQFNV SNDSNKWKFL EMFRSSSQNE 150
    FYNRRTLTSD TRFVGILKYG GRVWTFHGET PRATTDSSST ANLNNISITI 200
    HSEFYIIPRS QESKCNEYIN NGLPPIQNTR NVVPLPLSSR SIQYKRAQVN 250
    EDIIVSKTSL WKEMQYNRDI IIRFKFGNSI VKMGGLGYKW SEISYKAANY 300
    QYNYLRDGEQ VTAHTTCSVN GVNNFSYNGG SLPTDFGISR YEVIKENSYV 350
    YVDYWDDSKA FRNMVYVRSL AANLNSVKCT GGSYNFSIPV GAWPVMNGGA 400
    VSLHFAGVTL STQFTDFVSL NSLRFRFSLT VDEPPFSILR TRTVNLYGLP 450
    AANPNNGNEY YEISGRFSLI YLVPTNDDYQ TPIMNSVTVR QDLERQLTDL 500
    REEFNSLSQE IAMAQLIDLA LLPLDMFSMF SGIKSTIDLT KSMATSVMKK 550
    FRKSKLATSI SEMTNSLSDA ASSASRNVSI RSNLSAISNW TNVSNDVSNV 600
    TNSLNDISTQ TSTISKKFRL KEMITQTEGM SFDDISAAVL KTKIDMSTQI 650
    GKNTLPDIVT EASEKFIPKR SYRILKDDEV MEINTEGKFF AYKINTFDEV 700
    PFDVNKFAEL VTDSPVISAI IDFKTLKNLN DNYGITRTEA LNLIKSNPNM 750
    LRNFINQNNP IIRNRIEQLI LQCKL 775
    Length:775
    Mass (Da):87,697
    Last modified:April 14, 2009 - v3
    Checksum:i1CE181B859F74FB0
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti64 – 641I → M in AAA66953. (PubMed:7530390)Curated
    Sequence conflicti100 – 1001D → E(PubMed:3018754)Curated
    Sequence conflicti120 – 1201T → L(PubMed:2839714)Curated
    Sequence conflicti265 – 2651Q → E(PubMed:3018754)Curated
    Sequence conflicti331 – 3311S → F in AAA66953. (PubMed:7530390)Curated
    Sequence conflicti388 – 3881I → L in AAA47290. (PubMed:8389116)Curated
    Sequence conflicti525 – 5251D → G in AAA47290. (PubMed:8389116)Curated
    Sequence conflicti618 – 6181F → L(PubMed:2839714)Curated
    Sequence conflicti749 – 7491N → K(PubMed:2839714)Curated
    Sequence conflicti759 – 7591N → H(PubMed:2839714)Curated
    Sequence conflicti774 – 7741K → R(PubMed:2839714)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M96825 Genomic RNA. Translation: AAA47290.1.
    L34161 Genomic RNA. Translation: AAA66953.1.
    PIRiA28839. VPXRW3.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M96825 Genomic RNA. Translation: AAA47290.1 .
    L34161 Genomic RNA. Translation: AAA66953.1 .
    PIRi A28839. VPXRW3.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2DWR X-ray 2.50 A 65-223 [» ]
    ModBasei Search...
    MobiDBi Search...

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Miscellaneous databases

    EvolutionaryTracei P11193.

    Family and domain databases

    Gene3Di 2.60.120.200. 1 hit.
    InterProi IPR008985. ConA-like_lec_gl_sf.
    IPR013320. ConA-like_subgrp.
    IPR000416. Haemagglutinin_VP4.
    [Graphical view ]
    Pfami PF00426. VP4_haemagglut. 1 hit.
    [Graphical view ]
    SUPFAMi SSF49899. SSF49899. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "Sequence of the fourth gene of human rotaviruses recovered from asymptomatic or symptomatic infections."
      Gorziglia M., Green K.Y., Nishikawa K., Taniguchi K., Jones R.W., Kapikian A.Z., Chanock R.M.
      J. Virol. 62:2978-2984(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE.
    2. "Alterations in the sequence of the gene 4 from a human rotavirus after multiple passages in HepG2 liver cells."
      Kitamoto N., Mattion N.M., Estes M.K.
      Arch. Virol. 130:179-185(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    3. "Identification of two independent neutralization domains on the VP4 trypsin cleavage products VP5* and VP8* of human rotavirus ST3."
      Padilla-Noriega L., Dunn S.J., Lopez S., Greenberg H.B., Arias C.F.
      Virology 206:148-154(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    4. "Conservation of amino acid sequence of VP8 and cleavage region of 84-kDa outer capsid protein among rotaviruses recovered from asymptomatic neonatal infection."
      Gorziglia M., Hoshino Y., Buckler-White A., Blumentals I., Glass R., Flores J., Kapikian A.Z., Chanock R.M.
      Proc. Natl. Acad. Sci. U.S.A. 83:7039-7043(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-280.
    5. "Rotaviruses interact with alpha4beta7 and alpha4beta1 integrins by binding the same integrin domains as natural ligands."
      Graham K.L., Fleming F.E., Halasz P., Hewish M.J., Nagesha H.S., Holmes I.H., Takada Y., Coulson B.S.
      J. Gen. Virol. 86:3397-3408(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HUMAN INTEGRIN HETERODIMER ITGA4/ITGB1, INTERACTION WITH HUMAN INTEGRIN HETERODIMER ITGA4/ITGB7.
    6. "Rotavirus spike protein VP5* binds alpha2beta1 integrin on the cell surface and competes with virus for cell binding and infectivity."
      Graham K.L., Takada Y., Coulson B.S.
      J. Gen. Virol. 87:1275-1283(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HUMAN INTEGRIN HETERODIMER ITGA2/ITGB1.
    7. "Insight into host cell carbohydrate-recognition by human and porcine rotavirus from crystal structures of the virion spike associated carbohydrate-binding domain (VP8*)."
      Blanchard H., Yu X., Coulson B.S., von Itzstein M.
      J. Mol. Biol. 367:1215-1226(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 64-223.

    Entry informationi

    Entry nameiVP4_ROTHW
    AccessioniPrimary (citable) accession number: P11193
    Secondary accession number(s): Q05334, Q86202
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 1, 1989
    Last sequence update: April 14, 2009
    Last modified: October 1, 2014
    This is version 98 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programViral Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    In group A rotaviruses, VP4 defines the P serotype.
    This strain has been shown to be sialic acid-independent, and integrin-dependent in cell culture conditions.

    Keywords - Technical termi

    3D-structure, Complete proteome

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3