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Protein

Outer capsid protein VP4

Gene
N/A
Organism
Rotavirus A (isolate RVA/Cow/India/Hg18/2000/G15P[21]) (RV-A)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at transcript leveli

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

GO - Biological processi

Complete GO annotation...

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 (isolate RVA/Cow/India/Hg18/2000/G15P[21]) (RV-A)
Taxonomic identifieri141270 [NCBI]
Taxonomic lineageiVirusesdsRNA virusesReoviridaeSedoreovirinaeRotavirusRotavirus A
Virus hostiBos taurus (Bovine) [TaxID: 9913]

Subcellular locationi

Outer capsid protein VP4 :
  • Virion By similarity
  • 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 (By similarity).By similarity
Outer capsid protein VP8* :
  • Virion

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

  • Note: Outer capsid protein.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003680891 – 776Outer capsid protein VP4Add BLAST776
ChainiPRO_00003680901 – 231Outer capsid protein VP8*Add BLAST231
ChainiPRO_0000368091248 – 776Outer capsid protein VP5*Add BLAST529

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi32N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi56N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi97N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi132N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi278N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi311N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi318 ↔ 380Sequence analysis
Glycosylationi593N-linked (GlcNAc...); by hostSequence analysis1

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei231 – 232CleavageBy similarity2
Sitei247 – 248CleavageSequence analysis2

Keywords - PTMi

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

ProteinModelPortaliQ9E780.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni248 – 480Antigen domainBy similarityAdd BLAST233
Regioni308 – 310DGE motif; interaction with ITGA2/ITGB1 heterodimerBy similarity3
Regioni389 – 409Hydrophobic; possible role in virus entry into host cellSequence analysisAdd BLAST21

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili484 – 518Sequence analysisAdd BLAST35

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi560 – 616Ser-richAdd BLAST57

Sequence similaritiesi

Belongs to the rotavirus VP4 family.Curated

Keywords - Domaini

Coiled coil

Family and domain databases

Gene3Di2.60.120.200. 1 hit.
InterProiIPR013320. ConA-like_dom.
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.

Q9E780-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGSFIYKQLL TNSYTVELSD EIDAIGSEKT QNVTINPGPF AQTGYAPVEW
60 70 80 90 100
GAGETNDSTT IEPVLDGPYQ PTRFNPEIGY WILLAPETQG IVLETTNTTN
110 120 130 140 150
KWFATILIEQ DVVAESRTYT IFGKTESIQA ENTSQTEWKF IDIIKTTQDG
160 170 180 190 200
TYSQYGPLVL STKLYGVMKY GGRLYAYIGH TPNATPGHYT IANYDTMEMS
210 220 230 240 250
IFCEFYIMPR SQEAQCTEYI NSGLPPIQNT RNIVPLSLSS RSIKYQKAQV
260 270 280 290 300
NEDIIISKTS LWKEMQYNID IIIRFKFNNS IIKSGGLGYK WLEIAFKPAN
310 320 330 340 350
YQYNYIRDGE NITAHTTCSV NGVNEFSYNG GSLPTDFAIS RYEVIKENSY
360 370 380 390 400
VYVDYWDDSQ AFRNMVYVRS LAANLNTVIC NGGDYSFQVP VGQWPVMSGG
410 420 430 440 450
AVSLQSAGVT LSTQFTDFVS LNSLRFRFSL AVESPPFSIT RTRVSNLYGL
460 470 480 490 500
PAANPNGGRD FYEILGRFSL ISLVPSNDDY QTPIMNSVTV RQDLDRQLGE
510 520 530 540 550
LRDEFNALSQ QIAMSQLIDL ALLPLDMFSM FSGIKGSIDV ARSMATKVMK
560 570 580 590 600
KFRNSKLASS VSTLTDSLSD AASSLSRTST IRSIGSSASA WTNISSQVDD
610 620 630 640 650
VISSTSEIST QTSTISRRLR VKEIATQTEG MNFDDISAAV LKAKIDRSTQ
660 670 680 690 700
IDSNTLPDIV TEASEKFIPN RAYRVMDGDE VLEASTDGKF FAYKVETFDE
710 720 730 740 750
VPFDVQKFAD LVTDSPVISA IIDFKTLKNL NDNYGITKAQ AFNLLRSDPR
760 770
VLREFINQEN PIIRNRIEQL ILQCKL
Length:776
Mass (Da):86,745
Last modified:March 1, 2001 - v1
Checksum:i440AC1ADA2A715EE
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF237665 mRNA. Translation: AAG29806.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF237665 mRNA. Translation: AAG29806.1.

3D structure databases

ProteinModelPortaliQ9E780.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Family and domain databases

Gene3Di2.60.120.200. 1 hit.
InterProiIPR013320. ConA-like_dom.
IPR000416. Haemagglutinin_VP4.
[Graphical view]
PfamiPF00426. VP4_haemagglut. 1 hit.
[Graphical view]
SUPFAMiSSF49899. SSF49899. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiVP4_ROT18
AccessioniPrimary (citable) accession number: Q9E780
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 14, 2009
Last sequence update: March 1, 2001
Last modified: November 30, 2016
This is version 75 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.

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.