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P11193

- VP4_ROTHW

UniProt

P11193 - VP4_ROTHW

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Protein
Outer capsid protein VP4
Gene
N/A
Organism
Rotavirus A (strain Human/United States/Wa/1974 G1-P1A[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1) (RV-A)
Status
Reviewed - Annotation score: 4 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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei230 – 2312Cleavage By similarity
Sitei246 – 2472Cleavage By similarity

GO - Biological processi

  1. permeabilization of host organelle membrane involved in viral entry into host cell Source: UniProtKB-KW
  2. virion attachment to host cell Source: UniProtKB-KW
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 Human/United States/Wa/1974 G1-P1A[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1) (RV-A)
Taxonomic identifieri10962 [NCBI]
Taxonomic lineageiVirusesdsRNA virusesReoviridaeSedoreovirinaeRotavirusRotavirus A
Virus hostiHomo sapiens (Human) [TaxID: 9606]
ProteomesiUP000006581: Genome

Subcellular locationi

Chain Outer capsid protein VP4 : Virion. Host rough endoplasmic reticulum Reviewed prediction
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.
Chain Outer capsid protein VP8* : Virion
Note: Outer capsid protein By similarity.
Chain Outer capsid protein VP5* : Virion
Note: Outer capsid protein By similarity.

GO - Cellular componenti

  1. host cell rough endoplasmic reticulum Source: UniProtKB-SubCell
  2. viral outer capsid Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 775775Outer capsid protein VP4
PRO_0000041090Add
BLAST
Chaini1 – 230230Outer capsid protein VP8* By similarity
PRO_0000041091Add
BLAST
Chaini247 – 775529Outer capsid protein VP5* By similarity
PRO_0000041092Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi32 – 321N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi56 – 561N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi97 – 971N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi129 – 1291N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi132 – 1321N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi195 – 1951N-linked (GlcNAc...); by host Reviewed prediction
Disulfide bondi317 ↔ 379 Reviewed prediction
Glycosylationi324 – 3241N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi385 – 3851N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi577 – 5771N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi583 – 5831N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi589 – 5891N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi592 – 5921N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi599 – 5991N-linked (GlcNAc...); by host Reviewed prediction

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.

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Interactioni

Subunit structurei

VP4 is a homotrimer Reviewed prediction. 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 Reviewed prediction. 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.2 Publications

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi66 – 694
Beta strandi71 – 744
Beta strandi80 – 856
Beta strandi88 – 969
Beta strandi98 – 1003
Beta strandi102 – 1087
Beta strandi110 – 12112
Beta strandi124 – 1329
Beta strandi134 – 14613
Beta strandi152 – 16110
Beta strandi163 – 1697
Beta strandi172 – 1798
Beta strandi184 – 1896
Beta strandi197 – 2004
Beta strandi204 – 2085
Helixi209 – 2113
Helixi212 – 22110

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2DWRX-ray2.50A65-223[»]

Miscellaneous databases

EvolutionaryTraceiP11193.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni247 – 479233Antigen domain
Add
BLAST
Regioni307 – 3093DGE motif; interaction with ITGA2/ITGB1 heterodimer Inferred
Regioni388 – 40821Hydrophobic; possible role in virus entry into host cell Reviewed prediction
Add
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili483 – 51735 Reviewed prediction
Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi559 – 61557Ser-rich
Add
BLAST

Sequence similaritiesi

Belongs to the rotavirus VP4 family.

Keywords - Domaini

Coiled coil

Family and domain databases

Gene3Di2.60.120.200. 1 hit.
InterProiIPR008985. ConA-like_lec_gl_sf.
IPR013320. ConA-like_subgrp.
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

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MASLIYRQLL TNSYSVDLHD EIEQIGSEKT QNVTINPSPF AQTRYAPVNW    50
GHGEINDSTT VEPILDGPYQ PTTFTPPNDY WILINSNTNG VVYESTNNSD 100
FWTAVVAIEP HVNPVDRQYT IFGESKQFNV SNDSNKWKFL EMFRSSSQNE 150
FYNRRTLTSD TRFVGILKYG GRVWTFHGET PRATTDSSST ANLNNISITI 200
HSEFYIIPRS QESKCNEYIN NGLPPIQNTR NVVPLPLSSR SIQYKRAQVN 250
EDIIVSKTSL WKEMQYNRDI IIRFKFGNSI VKMGGLGYKW SEISYKAANY 300
QYNYLRDGEQ VTAHTTCSVN GVNNFSYNGG SLPTDFGISR YEVIKENSYV 350
YVDYWDDSKA FRNMVYVRSL AANLNSVKCT GGSYNFSIPV GAWPVMNGGA 400
VSLHFAGVTL STQFTDFVSL NSLRFRFSLT VDEPPFSILR TRTVNLYGLP 450
AANPNNGNEY YEISGRFSLI YLVPTNDDYQ TPIMNSVTVR QDLERQLTDL 500
REEFNSLSQE IAMAQLIDLA LLPLDMFSMF SGIKSTIDLT KSMATSVMKK 550
FRKSKLATSI SEMTNSLSDA ASSASRNVSI RSNLSAISNW TNVSNDVSNV 600
TNSLNDISTQ TSTISKKFRL KEMITQTEGM SFDDISAAVL KTKIDMSTQI 650
GKNTLPDIVT EASEKFIPKR SYRILKDDEV MEINTEGKFF AYKINTFDEV 700
PFDVNKFAEL VTDSPVISAI IDFKTLKNLN DNYGITRTEA LNLIKSNPNM 750
LRNFINQNNP IIRNRIEQLI LQCKL 775
Length:775
Mass (Da):87,697
Last modified:April 14, 2009 - v3
Checksum:i1CE181B859F74FB0
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti64 – 641I → M in AAA66953. 1 Publication
Sequence conflicti100 – 1001D → E1 Publication
Sequence conflicti120 – 1201T → L1 Publication
Sequence conflicti265 – 2651Q → E1 Publication
Sequence conflicti331 – 3311S → F in AAA66953. 1 Publication
Sequence conflicti388 – 3881I → L in AAA47290. 1 Publication
Sequence conflicti525 – 5251D → G in AAA47290. 1 Publication
Sequence conflicti618 – 6181F → L1 Publication
Sequence conflicti749 – 7491N → K1 Publication
Sequence conflicti759 – 7591N → H1 Publication
Sequence conflicti774 – 7741K → R1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M96825 Genomic RNA. Translation: AAA47290.1.
L34161 Genomic RNA. Translation: AAA66953.1.
PIRiA28839. VPXRW3.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M96825 Genomic RNA. Translation: AAA47290.1 .
L34161 Genomic RNA. Translation: AAA66953.1 .
PIRi A28839. VPXRW3.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2DWR X-ray 2.50 A 65-223 [» ]
ModBasei Search...
MobiDBi Search...

Protocols and materials databases

Structural Biology Knowledgebase Search...

Miscellaneous databases

EvolutionaryTracei P11193.

Family and domain databases

Gene3Di 2.60.120.200. 1 hit.
InterProi IPR008985. ConA-like_lec_gl_sf.
IPR013320. ConA-like_subgrp.
IPR000416. Haemagglutinin_VP4.
[Graphical view ]
Pfami PF00426. VP4_haemagglut. 1 hit.
[Graphical view ]
SUPFAMi SSF49899. SSF49899. 1 hit.
ProtoNeti Search...

Publicationsi

  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.
  2. "Alterations in the sequence of the gene 4 from a human rotavirus after multiple passages in HepG2 liver cells."
    Kitamoto N., Mattion N.M., Estes M.K.
    Arch. Virol. 130:179-185(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  3. "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].
  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.
  5. "Rotaviruses interact with alpha4beta7 and alpha4beta1 integrins by binding the same integrin domains as natural ligands."
    Graham K.L., Fleming F.E., Halasz P., Hewish M.J., Nagesha H.S., Holmes I.H., Takada Y., Coulson B.S.
    J. Gen. Virol. 86:3397-3408(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HUMAN INTEGRIN HETERODIMER ITGA4/ITGB1, INTERACTION WITH HUMAN INTEGRIN HETERODIMER ITGA4/ITGB7.
  6. "Rotavirus spike protein VP5* binds alpha2beta1 integrin on the cell surface and competes with virus for cell binding and infectivity."
    Graham K.L., Takada Y., Coulson B.S.
    J. Gen. Virol. 87:1275-1283(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HUMAN INTEGRIN HETERODIMER ITGA2/ITGB1.
  7. "Insight into host cell carbohydrate-recognition by human and porcine rotavirus from crystal structures of the virion spike associated carbohydrate-binding domain (VP8*)."
    Blanchard H., Yu X., Coulson B.S., von Itzstein M.
    J. Mol. Biol. 367:1215-1226(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 64-223.

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: February 19, 2014
This is version 97 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

External Data

Dasty 3

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