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P12976

- VP4_ROTS1

UniProt

P12976 - VP4_ROTS1

Protein

Outer capsid protein VP4

Gene
N/A
Organism
Rotavirus A (strain SA11-Both G3-P5B[2]-I2-R2-C5-M5-A5-N2-T5-E2-H5) (RV-A) (Simian Agent 11 (strain Both))
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 97 (01 Oct 2014)
      Sequence version 1 (01 Oct 1989)
      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 By similarity.By similarity
    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 By similarity.By similarity
    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
    Sitei231 – 2322CleavageBy similarity
    Sitei247 – 2482CleavageBy 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 SA11-Both G3-P5B[2]-I2-R2-C5-M5-A5-N2-T5-E2-H5) (RV-A) (Simian Agent 11 (strain Both))
    Taxonomic identifieri37137 [NCBI]
    Taxonomic lineageiVirusesdsRNA virusesReoviridaeSedoreovirinaeRotavirusRotavirus A
    Virus hostiMacaca mulatta (Rhesus macaque) [TaxID: 9544]
    ProteomesiUP000007180: 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 – 776776Outer capsid protein VP4PRO_0000041114Add
    BLAST
    Chaini1 – 231231Outer capsid protein VP8*By similarityPRO_0000041115Add
    BLAST
    Chaini248 – 776529Outer capsid protein VP5*By similarityPRO_0000041116Add
    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
    Glycosylationi116 – 1161N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi132 – 1321N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi149 – 1491N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi198 – 1981N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi203 ↔ 216Sequence Analysis
    Disulfide bondi318 ↔ 380Sequence Analysis
    Glycosylationi386 – 3861N-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

    3D structure databases

    ProteinModelPortaliP12976.
    SMRiP12976. Positions 64-224, 253-522.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni248 – 480233Antigen domainBy similarityAdd
    BLAST
    Regioni308 – 3103DGE motif; interaction with ITGA2/ITGB1 heterodimerBy similarity
    Regioni389 – 40921Hydrophobic; possible role in virus entry into host cellSequence AnalysisAdd
    BLAST

    Coiled coil

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Coiled coili484 – 51835Sequence AnalysisAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi308 – 3103DGE motif; interaction with ITGA2/ITGB1 heterodimerCurated

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi560 – 61657Ser-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.

    P12976-1 [UniParc]FASTAAdd to Basket

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    MASLIYRQLL TNSYTVDLSD EIQEIGSTKS QNVTINPGPF AQTGYAPVNW    50
    GPGEINDSTT VEPLLDGPYQ PTTFNPPVDY WMLLAPTTPG VIVEGTNNTD 100
    RWLATILIEP NVQSENRTYT IFGIQEQLTV SNTSQDQWKF IDVVKTTANG 150
    SIGQYGPLLS SPKLYAVMKH NEKLYTYEGQ TPNARTAHYS TTNYDSVNMT 200
    AFCDFYIIPR SEESKCTEYI NNGLPPIQNT RNVVPLSLTA RDVIHYRAQA 250
    NEDIVISKTS LWKEMQYNRD ITIRFKFANT IIKSGGLGYK WSEISFKPAN 300
    YQYTYTRDGE EVTAHTTCSV NGVNDFSFNG GYLPTDFVVS KFEVIKENSY 350
    VYIDYWDDSQ AFRNVVYVRS LAANLNSVMC TGGSYNFSLP VGQWPVLTGG 400
    AVSLHSAGVT LSTQFTDFVS LNSLRFRFRL AVEEPHFKLT RTRLDRLYGL 450
    PAADPNNGKE YYEIAGRFSL ISLVPSNDDY QTPIANSVTV RQDLERQLGE 500
    LREEFNALSQ EIAMSQLIDL ALLPLDMFSM FSGIKSTIDA AKSMATNVMK 550
    KFKKSGLANS VSTLTDSLSD AASSISRGSS IRSIGSSASA WTDVSTQITD 600
    ISSSVSSVST QTSTISRRLR LKEMATQTEG MNFDDISAAV LKTKIDKSTQ 650
    ISPNTIPDIV TEASEKFIPN RAYRVINNDD VFEAGIDGKF FAYKVDTFEE 700
    IPFDVQKFAD LVTDSPVISA IIDFKTLKNL NDNYGITKQQ AFNLLRSDPR 750
    VLREFINQDN PIIRNRIEQL IMQCRL 776
    Length:776
    Mass (Da):86,775
    Last modified:October 1, 1989 - v1
    Checksum:iEA9B43CE96CC53CF
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X14204 mRNA. Translation: CAA32420.1.
    PIRiS03611.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X14204 mRNA. Translation: CAA32420.1 .
    PIRi S03611.

    3D structure databases

    ProteinModelPortali P12976.
    SMRi P12976. Positions 64-224, 253-522.
    ModBasei Search...
    MobiDBi Search...

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    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. "Complete nucleotide sequence of the simian rotavirus SA11 VP4 gene."
      Mitchell D.B., Both G.W.
      Nucleic Acids Res. 17:2122-2122(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "Integrin-using rotaviruses bind alpha2beta1 integrin alpha2 I domain via VP4 DGE sequence and recognize alphaXbeta2 and alphaVbeta3 by using VP7 during cell entry."
      Graham K.L., Halasz P., Tan Y., Hewish M.J., Takada Y., Mackow E.R., Robinson M.K., Coulson B.S.
      J. Virol. 77:9969-9978(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HUMAN INTEGRIN ITGA2.
    3. "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.

    Entry informationi

    Entry nameiVP4_ROTS1
    AccessioniPrimary (citable) accession number: P12976
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1989
    Last sequence update: October 1, 1989
    Last modified: October 1, 2014
    This is version 97 of the entry and version 1 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-dependent, and integrin-dependent in cell culture conditions.By similarity

    Keywords - Technical termi

    Complete proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3