Hmdb loader
Identification
HMDB Protein ID HMDBP14397
Secondary Accession Numbers None
Name Outer capsid protein VP4
Synonyms
  1. Hemagglutinin
Gene Name Not Available
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function 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 attachment and entry into the host cell probably involves multiple sequential contacts between the outer capsid proteins VP4 and VP7, and the cell receptors. It is subsequently lost, together with VP7, following virus entry into the host cell. Following entry into the host cell, low intracellular or intravesicular Ca(2+) concentration probably causes the calcium-stabilized VP7 trimers to dissociate from the virion. This step is probably necessary for the membrane-disrupting entry step and the release of VP4, which is locked onto the virion by VP7. During the virus exit from the host cell, VP4 seems to be required to target the newly formed virions to the host cell lipid rafts.Forms the spike 'foot' and 'body' and acts as a membrane permeabilization protein that mediates release of viral particles from endosomal compartments into the cytoplasm. During entry, the part of VP5* that protrudes from the virus folds back on itself and reorganizes from a local dimer to a trimer. This reorganization may be linked to membrane penetration by exposing VP5* hydrophobic region. In integrin-dependent strains, VP5* targets the integrin heterodimer ITGA2/ITGB1 for cell attachment.Forms the head of the spikes and mediates the recognition of specific host cell surface glycans. 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. In some other strains, VP8* mediates the attachment to histo-blood group antigens (HBGAs) for viral entry.
Pathways Not Available
Reactions Not Available
GO Classification
Biological Process
virion attachment to host cell
permeabilization of host organelle membrane involved in viral entry into host cell
viral entry via permeabilization of inner membrane
Cellular Component
viral outer capsid
host cell endoplasmic reticulum-Golgi intermediate compartment
host cell rough endoplasmic reticulum
host cytoskeleton
host cell plasma membrane
membrane
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues Not Available
Molecular Weight 86773.735
Theoretical pI Not Available
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P12976
UniProtKB/Swiss-Prot Entry Name VP4_ROTS1
PDB IDs Not Available
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. Graham KL, Fleming FE, Halasz P, Hewish MJ, Nagesha HS, Holmes IH, Takada Y, Coulson BS: Rotaviruses interact with alpha4beta7 and alpha4beta1 integrins by binding the same integrin domains as natural ligands. J Gen Virol. 2005 Dec;86(Pt 12):3397-3408. doi: 10.1099/vir.0.81102-0. [PubMed:16298987 ]
  2. Mitchell DB, Both GW: Complete nucleotide sequence of the simian rotavirus SA11 VP4 gene. Nucleic Acids Res. 1989 Mar 11;17(5):2122. doi: 10.1093/nar/17.5.2122. [PubMed:2538804 ]
  3. Graham KL, Halasz P, Tan Y, Hewish MJ, Takada Y, Mackow ER, Robinson MK, Coulson BS: Integrin-using rotaviruses bind alpha2beta1 integrin alpha2 I domain via VP4 DGE sequence and recognize alphaXbeta2 and alphaVbeta3 by using VP7 during cell entry. J Virol. 2003 Sep;77(18):9969-78. doi: 10.1128/jvi.77.18.9969-9978.2003. [PubMed:12941907 ]