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P11200 (VP4_ROTHT) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 86. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | 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 Kingdom/ST3/1975 G4-P2A[6]-I1-R1-C1-M1-A1-N1-T1-E1-H1) (RV-A) (Rotavirus A (strain St. Thomas 3)) [Complete proteome]
Taxonomic identifier10960 [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 existenceInferred from homology

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 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.

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.

Subcellular location

Outer capsid protein VP4: Virion By similarity. 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 By similarity.

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 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 By similarity
PRO_0000368146
Chain1 – 230230Outer capsid protein VP8* Potential
PRO_0000041082
Chain247 – 775529Outer capsid protein VP5* Potential
PRO_0000041083

Regions

Region247 – 479233Antigen domain By similarity
Region307 – 3093DGE motif; interaction with ITGA2/ITGB1 heterodimer By similarity
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
Glycosylation1111N-linked (GlcNAc...); by host Potential
Glycosylation1141N-linked (GlcNAc...); by host Potential
Glycosylation1321N-linked (GlcNAc...); by host Potential
Glycosylation1921N-linked (GlcNAc...); by host Potential
Glycosylation2771N-linked (GlcNAc...); by host Potential
Glycosylation3241N-linked (GlcNAc...); by host Potential
Glycosylation5831N-linked (GlcNAc...); by host Potential
Glycosylation6061N-linked (GlcNAc...); by host Potential
Disulfide bond317 ↔ 379 Potential

Experimental info

Sequence conflict49 – 535TWSHG → VLESW Ref.1
Sequence conflict49 – 535TWSHG → VLESW Ref.4
Sequence conflict701Q → R in AAA66952. Ref.2
Sequence conflict1301I → V Ref.1
Sequence conflict1301I → V Ref.4
Sequence conflict1461N → S Ref.1
Sequence conflict1461N → S Ref.4
Sequence conflict1751T → S Ref.1
Sequence conflict1751T → S Ref.4
Sequence conflict1901T → A in ABV53292. Ref.3
Sequence conflict2501S → N Ref.1
Sequence conflict2501S → N Ref.4
Sequence conflict3161T → I in ABV53292. Ref.3
Sequence conflict3311L → S in AAA66952. Ref.2
Sequence conflict3351H → D in ABV53292. Ref.3
Sequence conflict3381I → V Ref.1
Sequence conflict3531D → N Ref.1
Sequence conflict3611F → L Ref.1
Sequence conflict3881M → L Ref.1
Sequence conflict4131Q → K Ref.1
Sequence conflict4741P → L in AAA66952. Ref.2
Sequence conflict5651G → R Ref.1
Sequence conflict5891E → V Ref.2
Sequence conflict5891E → V in ABV53292. Ref.3
Sequence conflict6141Missing Ref.1
Sequence conflict6321D → I Ref.1
Sequence conflict7321N → T in ABV53292. Ref.3

Sequences

Sequence LengthMass (Da)Tools
P11200 [UniParc].

Last modified April 14, 2009. Version 3.
Checksum: 1F9E5AA8C35BE7DD

FASTA77587,487
        10         20         30         40         50         60 
MASLIYRQLL TNSYTVELSD EINTIGSEKS QNITINPGPF AQTNYAPVTW SHGEVNDSTT 

        70         80         90        100        110        120 
IEPVLDGPYQ PTSFKPPSDY WILLNPTNQQ VVLEGTNKTD IWIALLLVEP NVTNQSRQYT 

       130        140        150        160        170        180 
LFGETKQITI ENNTNKWKFF EMFRSNVSSE FQHKRTLTSD TKLAGFLKHY NSVWTFHGET 

       190        200        210        220        230        240 
PHATTDYSST SNLSEVETTI HVEFYIISRS QESKCVEYIN TGLPPMQNTR NIVPVALSSR 

       250        260        270        280        290        300 
SVTYQRAQVS EDIIISKTSL WKEMQYNRDI IIRFKFNNSI IKLGGLGYKW SEISFKAANY 

       310        320        330        340        350        360 
QYNYLRDGEQ VTAHTTCSVN GVNNFSYNGG LLPTHFSISR YEVIKENSYV YVDYWDDSQA 

       370        380        390        400        410        420 
FRNMVYVRSL AANLNSVKCS GGNYNFQMPV GAWPVMSGGA VSLHFAGVTL STQFTDFVSL 

       430        440        450        460        470        480 
NSLRFRFSLT VEEPPFSILR TRVSGLYGLP ASNPNSGHEY YEIAGRFSLI SLVPSNDDYQ 

       490        500        510        520        530        540 
TPIMNSITVR QDLERQLGDL REEFNSLSQE IAITQLIDLA LLPLDMFSMF SGIKSTIDAA 

       550        560        570        580        590        600 
KSMATKVMKK FKRSGLATSI SELTGSLSNA ASSVSRSSSI RSNISSISEW TDVSEQIAGS 

       610        620        630        640        650        660 
SDSVRNISTQ TSAISRRLRL REITTQTEGM NDIDISAAVL KTKIDRSTHI RPDTLPDIIT 

       670        680        690        700        710        720 
ESSEKFIPKR AYRVLKDDEV MEADVDGKFF AYKVDTFEEV PFDVDKFVDL VTDSPVISAI 

       730        740        750        760        770 
IDFKTLKNLN DNYGITRSQA LDLIRSDPRV LRDFINQNNP IIKNRIEQLI LQCRL 

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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 [GENOMIC RNA].
[2]"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].
[3]"Group A human rotavirus genomics: evidence that gene constellations are influenced by viral protein interactions."
Heiman E.M., McDonald S.M., Barro M., Taraporewala Z.F., Bar-Magen T., Patton J.T.
J. Virol. 82:11106-11116(2008) [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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L33895 Genomic RNA. Translation: AAA66952.1.
EF672612 Genomic RNA. Translation: ABV53292.1.
PIRVPXRWT. H28839.

3D structure databases

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...

Entry information

Entry nameVP4_ROTHT
AccessionPrimary (citable) accession number: P11200
Secondary accession number(s): B3SRW7, Q86201
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: April 14, 2009
Last modified: February 19, 2014
This is version 86 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