Q83440 (VP4_ROTMB) Reviewed, UniProtKB/Swiss-Prot
Last modified February 19, 2014. Version 72. History...
Names and origin
|Protein names||Recommended name:|
Outer capsid protein VP4
|Organism||Rotavirus A (isolate Mouse/United States/Eb/1982 G16-P10-Ix-Rx-Cx-Mx-Ax-Nx-Tx-E7-Hx) (RV-A)|
|Taxonomic identifier||578842 [NCBI]|
|Taxonomic lineage||Viruses › dsRNA viruses › Reoviridae › Sedoreovirinae › Rotavirus › Rotavirus A ›|
|Virus host||Mus musculus musculus (eastern European house mouse) [TaxID: 39442]|
|Sequence length||775 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Inferred from homology|
General annotation (Comments)
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.
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.
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.
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.
Outer capsid protein VP4: Virion By similarity. Host rough endoplasmic reticulum Potential. 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.
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.
In group A rotaviruses, VP4 defines the P serotype.
This strain has been shown to be sialic acid-independent in cell culture conditions By similarity.
Belongs to the rotavirus VP4 family.
|Biological process||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
|Cellular component||Host endoplasmic reticulum|
|Molecular function||Capsid protein|
Outer capsid protein
|Gene Ontology (GO)|
|Biological_process||permeabilization of host organelle membrane involved in viral entry into host cell|
Inferred from electronic annotation. Source: UniProtKB-KWvirion attachment to host cell
Inferred from electronic annotation. Source: UniProtKB-KW
|Cellular_component||host cell rough endoplasmic reticulum|
Inferred from electronic annotation. Source: UniProtKB-SubCellviral outer capsid
Inferred from electronic annotation. Source: UniProtKB-KW
|Complete GO annotation...|
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 775||775||Outer capsid protein VP4||PRO_0000368125|
|Chain||1 – 230||230||Outer capsid protein VP8*||PRO_0000368126|
|Chain||247 – 775||529||Outer capsid protein VP5*||PRO_0000368127|
|Region||247 – 479||233||Antigen domain By similarity|
|Region||307 – 309||3||DGE motif; interaction with ITGA2/ITGB1 heterodimer By similarity|
|Region||388 – 408||21||Hydrophobic; possible role in virus entry into host cell Potential|
|Coiled coil||483 – 517||35||Potential|
|Compositional bias||559 – 615||57||Ser-rich|
|Site||230 – 231||2||Cleavage By similarity|
|Site||246 – 247||2||Cleavage By similarity|
Amino acid modifications
|Glycosylation||32||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||57||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||111||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||149||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||197||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||669||1||N-linked (GlcNAc...); by host Potential|
|Disulfide bond||317 ↔ 379||Potential|
|Sequence conflict||46||1||A → P in AAA47356. Ref.2|
|Sequence conflict||218||1||Y → S in AAA47356. Ref.2|
|Sequence conflict||234||1||A → S in AAA47356. Ref.2|
|Sequence conflict||253 – 254||2||IV → RC in AAA47356. Ref.2|
|Sequence conflict||269||1||D → N in AAA47356. Ref.2|
|Sequence conflict||504||1||F → C in AAA47356. Ref.2|
|Sequence conflict||537||1||L → F in AAA47356. Ref.2|
|Sequence conflict||558||1||T → A in AAA47356. Ref.2|
|Sequence conflict||615 – 616||2||SR → RQ in AAA47356. Ref.2|
|Sequence conflict||666||1||F → L in AAA47356. Ref.2|
|Sequence conflict||674 – 675||2||II → TT in AAA47356. Ref.2|
|Sequence conflict||749||1||R → G in AAA47356. Ref.2|
|||"Comparison of VP4 and VP7 of five murine rotavirus strains."|
Dunn S.J., Burns J.W., Cross T.L., Vo P.T., Ward R.L., Bremont M., Greenberg H.B.
Virology 203:250-259(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
|||"The outer capsid protein VP4 of murine rotavirus strain Eb represents a tentative new P type."|
Sereno M.M., Gorziglia M.I.
Virology 199:500-504(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
|U08419 Genomic RNA. Translation: AAA50482.1.|
L18992 Genomic DNA. Translation: AAA47356.1. Frameshift.
3D structure databases
|SMR||Q83440. Positions 65-223, 252-521. |
Protocols and materials databases
Family and domain databases
|Gene3D||188.8.131.52. 1 hit. |
|InterPro||IPR008985. ConA-like_lec_gl_sf. |
|Pfam||PF00426. VP4_haemagglut. 1 hit. |
|SUPFAM||SSF49899. SSF49899. 1 hit. |
|Accession||Primary (citable) accession number: Q83440|
Secondary accession number(s): Q86227
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Viral Protein Annotation Program|
Index of protein domains and families