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Protein

Outer capsid protein VP4

Gene
N/A
Organism
Rotavirus A (strain RVA/Monkey/United States/RRV/1980/G3P5B[3]) (RV-A)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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. 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

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

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 RVA/Monkey/United States/RRV/1980/G3P5B[3]) (RV-A)
Taxonomic identifieri10969 [NCBI]
Taxonomic lineageiVirusesdsRNA virusesReoviridaeSedoreovirinaeRotavirusRotavirus A
Virus hostiMacaca mulatta (Rhesus macaque) [TaxID: 9544]

Subcellular locationi

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.
Outer capsid protein VP8* :
  • Virion

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

  • Note: Outer capsid protein.

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_00000411081 – 776Outer capsid protein VP4Add BLAST776
ChainiPRO_00000411091 – 231Outer capsid protein VP8*Sequence analysisAdd BLAST231
ChainiPRO_0000041110248 – 776Outer capsid protein VP5*Sequence analysisAdd 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
Glycosylationi111N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi149N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi183N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi198N-linked (GlcNAc...); by hostSequence analysis1
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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei231 – 232CleavageBy similarity2
Sitei247 – 248Cleavage2

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.Curated3 Publications

Structurei

Secondary structure

1776
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi66 – 69Combined sources4
Beta strandi71 – 74Combined sources4
Beta strandi80 – 84Combined sources5
Beta strandi88 – 96Combined sources9
Beta strandi98 – 100Combined sources3
Beta strandi102 – 108Combined sources7
Beta strandi110 – 121Combined sources12
Beta strandi124 – 132Combined sources9
Beta strandi135 – 147Combined sources13
Beta strandi153 – 162Combined sources10
Beta strandi165 – 170Combined sources6
Beta strandi173 – 180Combined sources8
Beta strandi185 – 190Combined sources6
Helixi194 – 196Combined sources3
Beta strandi198 – 203Combined sources6
Beta strandi205 – 209Combined sources5
Helixi210 – 212Combined sources3
Helixi213 – 222Combined sources10
Beta strandi249 – 258Combined sources10
Beta strandi260 – 275Combined sources16
Beta strandi278 – 283Combined sources6
Beta strandi290 – 297Combined sources8
Beta strandi299 – 307Combined sources9
Beta strandi310 – 322Combined sources13
Beta strandi324 – 329Combined sources6
Beta strandi338 – 345Combined sources8
Beta strandi350 – 359Combined sources10
Helixi360 – 362Combined sources3
Beta strandi367 – 375Combined sources9
Beta strandi378 – 381Combined sources4
Beta strandi384 – 386Combined sources3
Beta strandi390 – 392Combined sources3
Beta strandi396 – 399Combined sources4
Beta strandi401 – 415Combined sources15
Beta strandi420 – 432Combined sources13
Beta strandi437 – 439Combined sources3
Beta strandi449 – 454Combined sources6
Turni455 – 458Combined sources4
Beta strandi462 – 475Combined sources14
Helixi492 – 512Combined sources21
Turni513 – 519Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
SMRiP12473.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP12473.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni248 – 480Antigen domainAdd 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.

P12473-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASLIYRQLL TNSYTVDLSD EIQEIGSTKT QNVTINLGPF AQTGYAPVNW
60 70 80 90 100
GPGETNDSTT VEPVLDGPYQ PTSFNPPVDY WMLLAPTAAG VVVEGTNNTD
110 120 130 140 150
RWLATILVEP NVTSETRSYT LFGTQEQITI ANASQTQWKF IDVVKTTQNG
160 170 180 190 200
SYSQYGPLQS TPKLYAVMKH NGKIYTYNGE TPNVTTKYYS TTNYDSVNMT
210 220 230 240 250
AFCDFYIIPR EEESTCTEYI NNGLPPIQNT RNIVPLALSA RNIISHRAQA
260 270 280 290 300
NEDIVVSKTS LWKEMQYNRD ITIRFKFASS IVKSGGLGYK WSEISFKPAN
310 320 330 340 350
YQYTYTRDGE DVTAHTTCSV NGMNDFNFNG GSLPTDFIIS RYEVIKENSY
360 370 380 390 400
VYVDYWDDSQ AFRNMVYVRS LAANLNSVIC TGGDYSFALP VGQWPVMTGG
410 420 430 440 450
AVSLHSAGVT LSTQFTDFVS FNSLRFRFRL TVEEPSFSIT RTRVGGLYGL
460 470 480 490 500
PAAYPNNGKE YYEVAGRLSL ISLVPSNDDY QTPITNSVTV RQDLERQLGE
510 520 530 540 550
LREEFNALSQ EIAMSQLIYL ALLPLDMFSM FSGIKSTIDA AKSMATSVMK
560 570 580 590 600
KFKKSGLANS VSTLTDSLSD AASSISRGAS IRSVGSSASA WTDVSTQITD
610 620 630 640 650
VSSSVSSIST QTSTISRRLR LKEMATQTEG MNFDDISAAV LKTKIDRSTQ
660 670 680 690 700
ISPNTLPDIV TEASEKFIPN RAYRVINNDE VFEAGTDGRY FAYRVETFDE
710 720 730 740 750
IPFDVQKFAD LVTDSPVISA IIDFKTLKNL NDNYGISRQQ AFNLLRSDPR
760 770
VLREFINQDN PIIRNRIEQL IMQCRL
Length:776
Mass (Da):86,554
Last modified:March 24, 2009 - v2
Checksum:iC012EB9E3816A3F9
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti73S → T in AAK52093 (PubMed:11462006).Curated1
Sequence conflicti132N → Y in AAA47345 (PubMed:2829198).Curated1
Sequence conflicti311D → E in AAK52093 (PubMed:11462006).Curated1
Sequence conflicti338I → V in AAK52093 (PubMed:11462006).Curated1
Sequence conflicti421F → L in AAK52093 (PubMed:11462006).Curated1
Sequence conflicti445 – 446GG → SR in AAK52093 (PubMed:11462006).Curated2
Sequence conflicti454Y → N in AAK52093 (PubMed:11462006).Curated1
Sequence conflicti468L → F in AAK52093 (PubMed:11462006).Curated1
Sequence conflicti519Y → D in AAK52093 (PubMed:11462006).Curated1
Sequence conflicti690Y → F in AAK52093 (PubMed:11462006).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti109 – 110EP → VA in strain: Isolate MMU-18006. 2
Natural varianti146T → S in strain: Isolate MMU-18006. 1
Natural varianti166A → G in strain: Isolate MMU-18006. 1
Natural varianti235 – 240PLALSA → LALSAS in strain: Isolate MMU-18006. 6
Natural varianti244 – 245IS → TY in strain: Isolate MMU-18006. 2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
Links Updated
M18736 Genomic RNA. Translation: AAA47345.1.
AY033150 mRNA. Translation: AAK52093.1.
PIRiA31078. VPXRRH.
I25904. VPXRRR.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
SMRiP12473.
ModBaseiSearch...
MobiDBiSearch...

Protein family/group databases

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

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Miscellaneous databases

EvolutionaryTraceiP12473.

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_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: November 30, 2016
This is version 107 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

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.