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P11193 (VP4_ROTHW) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 97. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Outer capsid protein VP4
Alternative name(s):
Hemagglutinin

Cleaved into the following 2 chains:

  1. Outer capsid protein VP8*
  2. Outer capsid protein VP5*
OrganismRotavirus A (strain Human/United States/Wa/1974 G1-P1A[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1) (RV-A) [Complete proteome]
Taxonomic identifier10962 [NCBI]
Taxonomic lineageVirusesdsRNA virusesReoviridaeSedoreovirinaeRotavirusRotavirus A
Virus hostHomo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length775 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

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. Ref.5 Ref.6

Subcellular location

Outer capsid protein VP4: Virion. Host rough endoplasmic reticulum Potential. 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.

Outer capsid protein VP8*: Virion. Note: Outer capsid protein By similarity.

Outer capsid protein VP5*: Virion. Note: Outer capsid protein By similarity.

Post-translational modification

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.

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.

Sequence similarities

Belongs to the rotavirus VP4 family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 775775Outer capsid protein VP4
PRO_0000041090
Chain1 – 230230Outer capsid protein VP8* By similarity
PRO_0000041091
Chain247 – 775529Outer capsid protein VP5* By similarity
PRO_0000041092

Regions

Region247 – 479233Antigen domain
Region307 – 3093DGE motif; interaction with ITGA2/ITGB1 heterodimer Probable
Region388 – 40821Hydrophobic; possible role in virus entry into host cell Potential
Coiled coil483 – 51735 Potential
Compositional bias559 – 61557Ser-rich

Sites

Site230 – 2312Cleavage By similarity
Site246 – 2472Cleavage By similarity

Amino acid modifications

Glycosylation321N-linked (GlcNAc...); by host Potential
Glycosylation561N-linked (GlcNAc...); by host Potential
Glycosylation971N-linked (GlcNAc...); by host Potential
Glycosylation1291N-linked (GlcNAc...); by host Potential
Glycosylation1321N-linked (GlcNAc...); by host Potential
Glycosylation1951N-linked (GlcNAc...); by host Potential
Glycosylation3241N-linked (GlcNAc...); by host Potential
Glycosylation3851N-linked (GlcNAc...); by host Potential
Glycosylation5771N-linked (GlcNAc...); by host Potential
Glycosylation5831N-linked (GlcNAc...); by host Potential
Glycosylation5891N-linked (GlcNAc...); by host Potential
Glycosylation5921N-linked (GlcNAc...); by host Potential
Glycosylation5991N-linked (GlcNAc...); by host Potential
Disulfide bond317 ↔ 379 Potential

Experimental info

Sequence conflict641I → M in AAA66953. Ref.3
Sequence conflict1001D → E Ref.4
Sequence conflict1201T → L Ref.1
Sequence conflict2651Q → E Ref.4
Sequence conflict3311S → F in AAA66953. Ref.3
Sequence conflict3881I → L in AAA47290. Ref.2
Sequence conflict5251D → G in AAA47290. Ref.2
Sequence conflict6181F → L Ref.1
Sequence conflict7491N → K Ref.1
Sequence conflict7591N → H Ref.1
Sequence conflict7741K → R Ref.1

Secondary structure

................................. 775
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P11193 [UniParc].

Last modified April 14, 2009. Version 3.
Checksum: 1CE181B859F74FB0

FASTA77587,697
        10         20         30         40         50         60 
MASLIYRQLL TNSYSVDLHD EIEQIGSEKT QNVTINPSPF AQTRYAPVNW GHGEINDSTT 

        70         80         90        100        110        120 
VEPILDGPYQ PTTFTPPNDY WILINSNTNG VVYESTNNSD FWTAVVAIEP HVNPVDRQYT 

       130        140        150        160        170        180 
IFGESKQFNV SNDSNKWKFL EMFRSSSQNE FYNRRTLTSD TRFVGILKYG GRVWTFHGET 

       190        200        210        220        230        240 
PRATTDSSST ANLNNISITI HSEFYIIPRS QESKCNEYIN NGLPPIQNTR NVVPLPLSSR 

       250        260        270        280        290        300 
SIQYKRAQVN EDIIVSKTSL WKEMQYNRDI IIRFKFGNSI VKMGGLGYKW SEISYKAANY 

       310        320        330        340        350        360 
QYNYLRDGEQ VTAHTTCSVN GVNNFSYNGG SLPTDFGISR YEVIKENSYV YVDYWDDSKA 

       370        380        390        400        410        420 
FRNMVYVRSL AANLNSVKCT GGSYNFSIPV GAWPVMNGGA VSLHFAGVTL STQFTDFVSL 

       430        440        450        460        470        480 
NSLRFRFSLT VDEPPFSILR TRTVNLYGLP AANPNNGNEY YEISGRFSLI YLVPTNDDYQ 

       490        500        510        520        530        540 
TPIMNSVTVR QDLERQLTDL REEFNSLSQE IAMAQLIDLA LLPLDMFSMF SGIKSTIDLT 

       550        560        570        580        590        600 
KSMATSVMKK FRKSKLATSI SEMTNSLSDA ASSASRNVSI RSNLSAISNW TNVSNDVSNV 

       610        620        630        640        650        660 
TNSLNDISTQ TSTISKKFRL KEMITQTEGM SFDDISAAVL KTKIDMSTQI GKNTLPDIVT 

       670        680        690        700        710        720 
EASEKFIPKR SYRILKDDEV MEINTEGKFF AYKINTFDEV PFDVNKFAEL VTDSPVISAI 

       730        740        750        760        770 
IDFKTLKNLN DNYGITRTEA LNLIKSNPNM LRNFINQNNP IIRNRIEQLI LQCKL 

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References

[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M96825 Genomic RNA. Translation: AAA47290.1.
L34161 Genomic RNA. Translation: AAA66953.1.
PIRVPXRW3. A28839.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2DWRX-ray2.50A65-223[»]
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Family and domain databases

Gene3D2.60.120.200. 1 hit.
InterProIPR008985. ConA-like_lec_gl_sf.
IPR013320. ConA-like_subgrp.
IPR000416. Haemagglutinin_VP4.
[Graphical view]
PfamPF00426. VP4_haemagglut. 1 hit.
[Graphical view]
SUPFAMSSF49899. SSF49899. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceP11193.

Entry information

Entry nameVP4_ROTHW
AccessionPrimary (citable) accession number: P11193
Secondary accession number(s): Q05334, Q86202
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: April 14, 2009
Last modified: February 19, 2014
This is version 97 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references