| Identification |
|---|
| HMDB Protein ID
| HMDBP14279 |
| Secondary Accession Numbers
| None |
| Name
| Outer capsid protein VP4 |
| Synonyms
|
- 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.VP8* Forms the head of the spikes and mediates the recognition of specific host cell surface glycans (PubMed:17306299). It is the viral hemagglutinin and an important target of neutralizing antibodies (By similarity). In sialic acid-dependent strains, VP8* binds to host cell sialic acid, most probably a ganglioside, providing the initial contact (PubMed:24501414). In some other strains, VP8* mediates the attachment to histo-blood group antigens (HBGAs) for viral entry (By similarity). |
| Pathways
|
Not Available
|
| Reactions
| Not Available |
| GO Classification
|
| Biological Process |
| virion attachment, binding of host cell surface receptor |
| 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 |
| membrane |
| host cell plasma membrane |
| viral outer capsid |
| host cell endoplasmic reticulum-Golgi intermediate compartment |
| host cell rough endoplasmic reticulum |
| host cytoskeleton |
|
| 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
| 87695.9 |
| Theoretical pI
| Not Available |
| Pfam Domain Function
|
|
| Signals
|
Not Available
|
|
Transmembrane Regions
|
Not Available
|
| Protein Sequence
|
Not Available
|
| External Links |
|---|
| GenBank ID Protein
| Not Available |
| UniProtKB/Swiss-Prot ID
| P11193 |
| UniProtKB/Swiss-Prot Entry Name
| VP4_ROTHW |
| PDB IDs
|
|
| GenBank Gene ID
| Not Available |
| GeneCard ID
| Not Available |
| GenAtlas ID
| Not Available |
| HGNC ID
| Not Available |
| References |
|---|
| General References
| - Isa P, Arias CF, Lopez S: Role of sialic acids in rotavirus infection. Glycoconj J. 2006 Feb;23(1-2):27-37. doi: 10.1007/s10719-006-5435-y. [PubMed:16575520 ]
- Gorziglia M, Green K, Nishikawa K, Taniguchi K, Jones R, Kapikian AZ, Chanock RM: Sequence of the fourth gene of human rotaviruses recovered from asymptomatic or symptomatic infections. J Virol. 1988 Aug;62(8):2978-84. doi: 10.1128/JVI.62.8.2978-2984.1988. [PubMed:2839714 ]
- Gorziglia M, Hoshino Y, Buckler-White A, Blumentals I, Glass R, Flores J, Kapikian AZ, Chanock RM: Conservation of amino acid sequence of VP8 and cleavage region of 84-kDa outer capsid protein among rotaviruses recovered from asymptomatic neonatal infection. Proc Natl Acad Sci U S A. 1986 Sep;83(18):7039-43. doi: 10.1073/pnas.83.18.7039. [PubMed:3018754 ]
- Kitamoto N, Mattion NM, Estes MK: Alterations in the sequence of the gene 4 from a human rotavirus after multiple passages in HepG2 liver cells. Arch Virol. 1993;130(1-2):179-85. doi: 10.1007/BF01319006. [PubMed:8389116 ]
- Padilla-Noriega L, Dunn SJ, Lopez S, Greenberg HB, Arias CF: Identification of two independent neutralization domains on the VP4 trypsin cleavage products VP5* and VP8* of human rotavirus ST3. Virology. 1995 Jan 10;206(1):148-54. doi: 10.1016/s0042-6822(95)80029-8. [PubMed:7530390 ]
- 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 ]
- Graham KL, Takada Y, Coulson BS: Rotavirus spike protein VP5* binds alpha2beta1 integrin on the cell surface and competes with virus for cell binding and infectivity. J Gen Virol. 2006 May;87(Pt 5):1275-1283. doi: 10.1099/vir.0.81580-0. [PubMed:16603530 ]
- Fleming FE, Bohm R, Dang VT, Holloway G, Haselhorst T, Madge PD, Deveryshetty J, Yu X, Blanchard H, von Itzstein M, Coulson BS: Relative roles of GM1 ganglioside, N-acylneuraminic acids, and alpha2beta1 integrin in mediating rotavirus infection. J Virol. 2014 Apr;88(8):4558-71. doi: 10.1128/JVI.03431-13. Epub 2014 Feb 5. [PubMed:24501414 ]
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