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Protein

Outer capsid protein VP4

Gene
N/A
Organism
Rotavirus A (isolate RVA/Dog/United States/Cu-1/1982/G3P5A[3]) (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/Dog/United States/Cu-1/1982/G3P5A[3]) (RV-A)
Taxonomic identifieri101357 [NCBI]
Taxonomic lineageiVirusesdsRNA virusesReoviridaeSedoreovirinaeRotavirusRotavirus A
Virus hostiCanis lupus familiaris (Dog) (Canis familiaris) [TaxID: 9615]

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_00003680981 – 776Outer capsid protein VP4Add BLAST776
ChainiPRO_00003680991 – 231Outer capsid protein VP8*Add BLAST231
ChainiPRO_0000368100248 – 776Outer capsid protein VP5*Add BLAST529

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi17N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi32N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi56N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi97N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi111N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi132N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi149N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi183N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi198N-linked (GlcNAc...); by hostSequence analysis1
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 (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

ProteinModelPortaliQ98637.
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.

Q98637-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASLIYRQLL TNSYTVNLSD EIQEIGSTKT QNITINPGPF AQTGYAPVNW
60 70 80 90 100
GPGETNDSTT IEPVLDGPYQ PTSFNPPVGY WMLLSPTAPG VVVEGTNNTD
110 120 130 140 150
RWLATILIEP NVTSQQRTYT IFGVQEQITV ENTSQTQWRF VDVSKTTQNG
160 170 180 190 200
SYSQYSPLLS TPKLYAVMKY GGRIHTYSGQ TPNATTGYYS ATNYDSVNMT
210 220 230 240 250
TFCDFYIIPR SEESKCTEYI NNGLPPIQNT RNIIPLALSA RNVRSLKAQS
260 270 280 290 300
NEDIVVSKTS LWKEMQYNRD ITIRFKFANS IVKSGGLGYK WSEISFKPAN
310 320 330 340 350
YQYTYMRDGE EVTAHTTCSV NGMNDFSFNG GSLPTDLLIS RYEVIKENSY
360 370 380 390 400
VYIDYWDDSQ AFRNMVYVRS LAANLNSVIC AGGHYNFALP VGQWPYMTGG
410 420 430 440 450
AVSLHSAGVT LSTQFTDFVS LNSLRFRFRL AVEEPSFAIM RTRVSGLYGL
460 470 480 490 500
PAANPNNGRE YYEIAGRFSL ISLIPSNDNY QTPIANSVTV RQDLERQLGE
510 520 530 540 550
LREEFNALSQ EIAMSQLIDL ALLPLDMFSM FSGIKSTIDA AKSIATNVMK
560 570 580 590 600
KFKKSSLASS VSTLTDSLSD AASSLSRGSS IRSVGSSVSA WTDVSTQITD
610 620 630 640 650
VSSSVSSIST QTSTISRRLR LKEMATQTEG MNFDDISAAV LKTKIDKSIQ
660 670 680 690 700
ISPNTLPDIV TEASEKFIPN RAYRVINNDE VFEASTDGRF FAYRVDTFEE
710 720 730 740 750
IPFDVQKFAD LVTDSPVISA IIDFKTLKNL NDNYGIGKQQ AFNLLRSDPK
760 770
VLREFINQNN PIIRNRIEQL IMQCRL
Length:776
Mass (Da):86,544
Last modified:February 1, 1997 - v1
Checksum:i5C7F489DFD791A36
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti113T → S in AAA47294 (PubMed:8277285).Curated1
Sequence conflicti242N → D in AAA47294 (PubMed:8277285).Curated1
Sequence conflicti337 – 338LL → FV in AAA47294 (PubMed:8277285).Curated2
Sequence conflicti384H → D in AAA47294 (PubMed:8277285).Curated1
Sequence conflicti685 – 686ST → GI in AAA47294 (PubMed:8277285).Curated2
Sequence conflicti772M → I in AAA47294 (PubMed:8277285).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D13401 mRNA. Translation: BAA02665.1.
L20876 mRNA. Translation: AAA47294.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D13401 mRNA. Translation: BAA02665.1.
L20876 mRNA. Translation: AAA47294.1.

3D structure databases

ProteinModelPortaliQ98637.
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_ROTCU
AccessioniPrimary (citable) accession number: Q98637
Secondary accession number(s): Q86170
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 14, 2009
Last sequence update: February 1, 1997
Last modified: November 30, 2016
This is version 86 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 in cell culture conditions.By similarity

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.