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P12473

- VP4_ROTRH

UniProt

P12473 - VP4_ROTRH

Protein

Outer capsid protein VP4

Gene
N/A
Organism
Rotavirus A (strain Monkey/United States/RRV/1980 G3-P5B[3]-I2-R2-C3-M3-A9-Nx-T3-E3-H6) (RV-A)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 102 (01 Oct 2014)
      Sequence version 2 (24 Mar 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. It is subsequently lost, together with VP7, following virus entry into the host cell. Rotavirus attachment and entry into the host cell probably involves multiple sequential contacts between the outer capsid proteins VP4 and VP7, and the cell receptors. In sialic acid-dependent and/or integrin-dependent strains, VP4 seems to essentially target sialic acid and/or the integrin heterodimer ITGA2/ITGB1.1 Publication
    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.1 Publication
    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.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei231 – 2322CleavageBy similarity
    Sitei247 – 2482Cleavage

    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

    Protein family/group databases

    TCDBi1.G.19.1.1. the rotavirus pore-forming membrane fusion complex (rotavirus mfc) family.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Outer capsid protein VP4
    Alternative name(s):
    Hemagglutinin
    Cleaved into the following 2 chains:
    OrganismiRotavirus A (strain Monkey/United States/RRV/1980 G3-P5B[3]-I2-R2-C3-M3-A9-Nx-T3-E3-H6) (RV-A)
    Taxonomic identifieri10969 [NCBI]
    Taxonomic lineageiVirusesdsRNA virusesReoviridaeSedoreovirinaeRotavirusRotavirus A
    Virus hostiMacaca mulatta (Rhesus macaque) [TaxID: 9544]

    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.
    Chain Outer capsid protein VP5* : Virion
    Note: Outer capsid protein.

    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_0000041108Add
    BLAST
    Chaini1 – 231231Outer capsid protein VP8*Sequence AnalysisPRO_0000041109Add
    BLAST
    Chaini248 – 776529Outer capsid protein VP5*Sequence AnalysisPRO_0000041110Add
    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
    Glycosylationi111 – 1111N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi149 – 1491N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi183 – 1831N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi198 – 1981N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi203 ↔ 216Sequence Analysis
    Disulfide bondi318 ↔ 380Sequence 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.1 Publication

    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/ITGB7.3 PublicationsCurated

    Structurei

    Secondary structure

    1
    776
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi66 – 694
    Beta strandi71 – 744
    Beta strandi80 – 845
    Beta strandi88 – 969
    Beta strandi98 – 1003
    Beta strandi102 – 1087
    Beta strandi110 – 12112
    Beta strandi124 – 1329
    Beta strandi135 – 14713
    Beta strandi153 – 16210
    Beta strandi165 – 1706
    Beta strandi173 – 1808
    Beta strandi185 – 1906
    Helixi194 – 1963
    Beta strandi198 – 2036
    Beta strandi205 – 2095
    Helixi210 – 2123
    Helixi213 – 22210
    Beta strandi249 – 25810
    Beta strandi260 – 27516
    Beta strandi278 – 2836
    Beta strandi290 – 2978
    Beta strandi299 – 3079
    Beta strandi310 – 32213
    Beta strandi324 – 3296
    Beta strandi338 – 3458
    Beta strandi350 – 35910
    Helixi360 – 3623
    Beta strandi367 – 3759
    Beta strandi378 – 3814
    Beta strandi384 – 3863
    Beta strandi390 – 3923
    Beta strandi396 – 3994
    Beta strandi401 – 41515
    Beta strandi420 – 43213
    Beta strandi437 – 4393
    Beta strandi449 – 4546
    Turni455 – 4584
    Beta strandi462 – 47514
    Helixi492 – 51221
    Turni513 – 5197

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1KQRX-ray1.40A62-224[»]
    1KRINMR-A46-231[»]
    1SLQX-ray3.20A/B/C/D/E/F248-525[»]
    2B4HX-ray1.60A/B248-479[»]
    2B4IX-ray2.00A/B/C248-479[»]
    2P3IX-ray1.75A64-224[»]
    2P3JX-ray1.90A64-224[»]
    2P3KX-ray1.56A64-224[»]
    3TB0X-ray2.00A64-224[»]
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP12473.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni248 – 480233Antigen domainAdd
    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

    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.

    P12473-1 [UniParc]FASTAAdd to Basket

    « Hide

    MASLIYRQLL TNSYTVDLSD EIQEIGSTKT QNVTINLGPF AQTGYAPVNW    50
    GPGETNDSTT VEPVLDGPYQ PTSFNPPVDY WMLLAPTAAG VVVEGTNNTD 100
    RWLATILVEP NVTSETRSYT LFGTQEQITI ANASQTQWKF IDVVKTTQNG 150
    SYSQYGPLQS TPKLYAVMKH NGKIYTYNGE TPNVTTKYYS TTNYDSVNMT 200
    AFCDFYIIPR EEESTCTEYI NNGLPPIQNT RNIVPLALSA RNIISHRAQA 250
    NEDIVVSKTS LWKEMQYNRD ITIRFKFASS IVKSGGLGYK WSEISFKPAN 300
    YQYTYTRDGE DVTAHTTCSV NGMNDFNFNG GSLPTDFIIS RYEVIKENSY 350
    VYVDYWDDSQ AFRNMVYVRS LAANLNSVIC TGGDYSFALP VGQWPVMTGG 400
    AVSLHSAGVT LSTQFTDFVS FNSLRFRFRL TVEEPSFSIT RTRVGGLYGL 450
    PAAYPNNGKE YYEVAGRLSL ISLVPSNDDY QTPITNSVTV RQDLERQLGE 500
    LREEFNALSQ EIAMSQLIYL ALLPLDMFSM FSGIKSTIDA AKSMATSVMK 550
    KFKKSGLANS VSTLTDSLSD AASSISRGAS IRSVGSSASA WTDVSTQITD 600
    VSSSVSSIST QTSTISRRLR LKEMATQTEG MNFDDISAAV LKTKIDRSTQ 650
    ISPNTLPDIV TEASEKFIPN RAYRVINNDE VFEAGTDGRY FAYRVETFDE 700
    IPFDVQKFAD LVTDSPVISA IIDFKTLKNL NDNYGISRQQ AFNLLRSDPR 750
    VLREFINQDN PIIRNRIEQL IMQCRL 776
    Length:776
    Mass (Da):86,554
    Last modified:March 24, 2009 - v2
    Checksum:iC012EB9E3816A3F9
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti73 – 731S → T in AAK52093. (PubMed:11462006)Curated
    Sequence conflicti132 – 1321N → Y in AAA47345. (PubMed:2829198)Curated
    Sequence conflicti311 – 3111D → E in AAK52093. (PubMed:11462006)Curated
    Sequence conflicti338 – 3381I → V in AAK52093. (PubMed:11462006)Curated
    Sequence conflicti421 – 4211F → L in AAK52093. (PubMed:11462006)Curated
    Sequence conflicti445 – 4462GG → SR in AAK52093. (PubMed:11462006)Curated
    Sequence conflicti454 – 4541Y → N in AAK52093. (PubMed:11462006)Curated
    Sequence conflicti468 – 4681L → F in AAK52093. (PubMed:11462006)Curated
    Sequence conflicti519 – 5191Y → D in AAK52093. (PubMed:11462006)Curated
    Sequence conflicti690 – 6901Y → F in AAK52093. (PubMed:11462006)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti109 – 1102EP → VA in strain: Isolate MMU-18006.
    Natural varianti146 – 1461T → S in strain: Isolate MMU-18006.
    Natural varianti166 – 1661A → G in strain: Isolate MMU-18006.
    Natural varianti235 – 2406PLALSA → LALSAS in strain: Isolate MMU-18006.
    Natural varianti244 – 2452IS → TY in strain: Isolate MMU-18006.

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M18736 Genomic RNA. Translation: AAA47345.1.
    AY033150 mRNA. Translation: AAK52093.1.
    PIRiA31078. VPXRRH.
    I25904. VPXRRR.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M18736 Genomic RNA. Translation: AAA47345.1 .
    AY033150 mRNA. Translation: AAK52093.1 .
    PIRi A31078. VPXRRH.
    I25904. VPXRRR.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1KQR X-ray 1.40 A 62-224 [» ]
    1KRI NMR - A 46-231 [» ]
    1SLQ X-ray 3.20 A/B/C/D/E/F 248-525 [» ]
    2B4H X-ray 1.60 A/B 248-479 [» ]
    2B4I X-ray 2.00 A/B/C 248-479 [» ]
    2P3I X-ray 1.75 A 64-224 [» ]
    2P3J X-ray 1.90 A 64-224 [» ]
    2P3K X-ray 1.56 A 64-224 [» ]
    3TB0 X-ray 2.00 A 64-224 [» ]
    ModBasei Search...
    MobiDBi Search...

    Protein family/group databases

    TCDBi 1.G.19.1.1. the rotavirus pore-forming membrane fusion complex (rotavirus mfc) family.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Miscellaneous databases

    EvolutionaryTracei P12473.

    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. "The rhesus rotavirus gene encoding protein VP3: location of amino acids involved in homologous and heterologous rotavirus neutralization and identification of a putative fusion region."
      Mackow E.R., Shaw R.D., Matsui S.M., Vo P.T., Dang M.-N., Greenberg H.G.
      Proc. Natl. Acad. Sci. U.S.A. 85:645-649(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    2. "Proteolysis of monomeric recombinant rotavirus VP4 yields an oligomeric VP5* core."
      Dormitzer P.R., Greenberg H.B., Harrison S.C.
      J. Virol. 75:7339-7350(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. "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 1-281.
      Strain: Isolate MMU-18006.
    4. "Location of intrachain disulfide bonds in the VP5* and VP8* trypsin cleavage fragments of the rhesus rotavirus spike protein VP4."
      Patton J.T., Hua J.J., Mansell E.A.
      J. Virol. 67:4848-4855(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISULFIDE BONDS.
    5. "Cleavage of rhesus rotavirus VP4 after arginine 247 is essential for rotavirus-like particle-induced fusion from without."
      Gilbert J.M., Greenberg H.B.
      J. Virol. 72:5323-5327(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEOLYTIC CLEAVAGE SITE.
    6. "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.
    7. "Alternative intermolecular contacts underlie the rotavirus VP5* two-to three-fold rearrangement."
      Yoder J.D., Dormitzer P.R.
      EMBO J. 25:1559-1568(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBUNIT.
    8. "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 SIMIAN INTEGRIN HETERODIMER ITGA2/ITGB1.
    9. "Effect of mutations in VP5 hydrophobic loops on rotavirus cell entry."
      Kim I.S., Trask S.D., Babyonyshev M., Dormitzer P.R., Harrison S.C.
      J. Virol. 84:6200-6207(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION OF VP5*.
    10. "The rhesus rotavirus VP4 sialic acid binding domain has a galectin fold with a novel carbohydrate binding site."
      Dormitzer P.R., Sun Z.Y., Wagner G., Harrison S.C.
      EMBO J. 21:885-897(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 62-224, STRUCTURE BY NMR OF 46-231.
    11. "Structural rearrangements in the membrane penetration protein of a non-enveloped virus."
      Dormitzer P.R., Nason E.B., Prasad B.V.V., Harrison S.C.
      Nature 430:1053-1058(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 248-525.
    12. "Rotavirus architecture at subnanometer resolution."
      Li Z., Baker M.L., Jiang W., Estes M.K., Prasad B.V.V.
      J. Virol. 83:1754-1766(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY ELECTRON CRYOMICROSCOPY OF CAPSID SHELL.

    Entry informationi

    Entry nameiVP4_ROTRH
    AccessioniPrimary (citable) accession number: P12473
    Secondary accession number(s): P11201
    , Q86214, Q86215, Q91HI9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1989
    Last sequence update: March 24, 2009
    Last modified: October 1, 2014
    This is version 102 of the entry and version 2 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.

    Keywords - Technical termi

    3D-structure

    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