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Protein

Outer capsid protein VP4

Gene
N/A
Organism
Rotavirus A (strain RVA/Human/United States/Wa/1974/G1P1A[8]) (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. 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).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 (strain RVA/Human/United States/Wa/1974/G1P1A[8]) (RV-A)
Taxonomic identifieri10962 [NCBI]
Taxonomic lineageiVirusesdsRNA virusesReoviridaeSedoreovirinaeRotavirusRotavirus A
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000006581 Componenti: Genome

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.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_00000410901 – 775Outer capsid protein VP4Add BLAST775
ChainiPRO_00000410911 – 230Outer capsid protein VP8*By similarityAdd BLAST230
ChainiPRO_0000041092247 – 775Outer capsid protein VP5*By similarityAdd 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
Glycosylationi129N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi132N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi195N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi317 ↔ 379Sequence analysis
Glycosylationi324N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi385N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi577N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi583N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi589N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi592N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi599N-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
Sitei230 – 231CleavageBy similarity2
Sitei246 – 247CleavageBy similarity2

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 (By similarity).By similarityCurated

Structurei

Secondary structure

1775
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 – 85Combined sources6
Beta strandi88 – 96Combined sources9
Beta strandi98 – 100Combined sources3
Beta strandi102 – 108Combined sources7
Beta strandi110 – 121Combined sources12
Beta strandi124 – 132Combined sources9
Beta strandi134 – 146Combined sources13
Beta strandi152 – 161Combined sources10
Beta strandi163 – 169Combined sources7
Beta strandi172 – 179Combined sources8
Beta strandi184 – 189Combined sources6
Beta strandi197 – 200Combined sources4
Beta strandi204 – 208Combined sources5
Helixi209 – 211Combined sources3
Helixi212 – 221Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DWRX-ray2.50A65-223[»]
SMRiP11193.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP11193.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni247 – 479Antigen domainAdd BLAST233
Regioni307 – 309DGE motif; interaction with ITGA2/ITGB1 heterodimerCurated3
Regioni388 – 408Hydrophobic; possible role in virus entry into host cellSequence analysisAdd BLAST21

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili483 – 517Sequence analysisAdd BLAST35

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi559 – 615Ser-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.

P11193-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASLIYRQLL TNSYSVDLHD EIEQIGSEKT QNVTINPSPF AQTRYAPVNW
60 70 80 90 100
GHGEINDSTT VEPILDGPYQ PTTFTPPNDY WILINSNTNG VVYESTNNSD
110 120 130 140 150
FWTAVVAIEP HVNPVDRQYT IFGESKQFNV SNDSNKWKFL EMFRSSSQNE
160 170 180 190 200
FYNRRTLTSD TRFVGILKYG GRVWTFHGET PRATTDSSST ANLNNISITI
210 220 230 240 250
HSEFYIIPRS QESKCNEYIN NGLPPIQNTR NVVPLPLSSR SIQYKRAQVN
260 270 280 290 300
EDIIVSKTSL WKEMQYNRDI IIRFKFGNSI VKMGGLGYKW SEISYKAANY
310 320 330 340 350
QYNYLRDGEQ VTAHTTCSVN GVNNFSYNGG SLPTDFGISR YEVIKENSYV
360 370 380 390 400
YVDYWDDSKA FRNMVYVRSL AANLNSVKCT GGSYNFSIPV GAWPVMNGGA
410 420 430 440 450
VSLHFAGVTL STQFTDFVSL NSLRFRFSLT VDEPPFSILR TRTVNLYGLP
460 470 480 490 500
AANPNNGNEY YEISGRFSLI YLVPTNDDYQ TPIMNSVTVR QDLERQLTDL
510 520 530 540 550
REEFNSLSQE IAMAQLIDLA LLPLDMFSMF SGIKSTIDLT KSMATSVMKK
560 570 580 590 600
FRKSKLATSI SEMTNSLSDA ASSASRNVSI RSNLSAISNW TNVSNDVSNV
610 620 630 640 650
TNSLNDISTQ TSTISKKFRL KEMITQTEGM SFDDISAAVL KTKIDMSTQI
660 670 680 690 700
GKNTLPDIVT EASEKFIPKR SYRILKDDEV MEINTEGKFF AYKINTFDEV
710 720 730 740 750
PFDVNKFAEL VTDSPVISAI IDFKTLKNLN DNYGITRTEA LNLIKSNPNM
760 770
LRNFINQNNP IIRNRIEQLI LQCKL
Length:775
Mass (Da):87,697
Last modified:April 14, 2009 - v3
Checksum:i1CE181B859F74FB0
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti64I → M in AAA66953 (PubMed:7530390).Curated1
Sequence conflicti100D → E (PubMed:3018754).Curated1
Sequence conflicti120T → L (PubMed:2839714).Curated1
Sequence conflicti265Q → E (PubMed:3018754).Curated1
Sequence conflicti331S → F in AAA66953 (PubMed:7530390).Curated1
Sequence conflicti388I → L in AAA47290 (PubMed:8389116).Curated1
Sequence conflicti525D → G in AAA47290 (PubMed:8389116).Curated1
Sequence conflicti618F → L (PubMed:2839714).Curated1
Sequence conflicti749N → K (PubMed:2839714).Curated1
Sequence conflicti759N → H (PubMed:2839714).Curated1
Sequence conflicti774K → R (PubMed:2839714).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M96825 Genomic RNA. Translation: AAA47290.1.
L34161 Genomic RNA. Translation: AAA66953.1.
PIRiA28839. VPXRW3.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M96825 Genomic RNA. Translation: AAA47290.1.
L34161 Genomic RNA. Translation: AAA66953.1.
PIRiA28839. VPXRW3.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DWRX-ray2.50A65-223[»]
SMRiP11193.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Miscellaneous databases

EvolutionaryTraceiP11193.

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_ROTHW
AccessioniPrimary (citable) accession number: P11193
Secondary accession number(s): Q05334, Q86202
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: April 14, 2009
Last modified: November 30, 2016
This is version 103 of the entry and version 3 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-independent, and integrin-dependent in cell culture conditions.

Keywords - Technical termi

3D-structure, Complete proteome

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.