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Showing Protein Outer capsid protein VP4 (HMDBP14429)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 0 metabolites
Identification
HMDB Protein ID HMDBP14429
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 (PubMed:25211455). 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 (PubMed:15165605). It is subsequently lost, together with VP7, following virus entry into the host cell (PubMed:15165605). 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 (PubMed:25211455). This step is probably necessary for the membrane-disrupting entry step and the release of VP4, which is locked onto the virion by VP7 (PubMed:25211455). 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 (PubMed:16571810).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 (PubMed:20375171). In some other strains, VP8* mediates the attachment to histo-blood group antigens (HBGAs) for viral entry (PubMed:29136651).
Pathways Not Available
Reactions Not Available
GO Classification
Biological Process
viral entry into host cell
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
viral outer capsid
host cell endoplasmic reticulum-Golgi intermediate compartment
host cell rough endoplasmic reticulum
host cytoskeleton
host cell plasma membrane
membrane
Molecular Function
sialic acid binding
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 86553.265
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 P12473
UniProtKB/Swiss-Prot Entry Name VP4_ROTRH
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. 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 ]
  2. Ciarlet M, Ludert JE, Iturriza-Gomara M, Liprandi F, Gray JJ, Desselberger U, Estes MK: Initial interaction of rotavirus strains with N-acetylneuraminic (sialic) acid residues on the cell surface correlates with VP4 genotype, not species of origin. J Virol. 2002 Apr;76(8):4087-95. doi: 10.1128/jvi.76.8.4087-4095.2002. [PubMed:11907248 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. Mackow ER, Shaw RD, Matsui SM, Vo PT, Dang MN, Greenberg HB: The rhesus rotavirus gene encoding protein VP3: location of amino acids involved in homologous and heterologous rotavirus neutralization and identification of a putative fusion region. Proc Natl Acad Sci U S A. 1988 Feb;85(3):645-9. doi: 10.1073/pnas.85.3.645. [PubMed:2829198 ]
  7. Dormitzer PR, Greenberg HB, Harrison SC: Proteolysis of monomeric recombinant rotavirus VP4 yields an oligomeric VP5* core. J Virol. 2001 Aug;75(16):7339-50. doi: 10.1128/JVI.75.16.7339-7350.2001. [PubMed:11462006 ]
  8. Patton JT, Hua J, Mansell EA: Location of intrachain disulfide bonds in the VP5* and VP8* trypsin cleavage fragments of the rhesus rotavirus spike protein VP4. J Virol. 1993 Aug;67(8):4848-55. doi: 10.1128/JVI.67.8.4848-4855.1993. [PubMed:8392619 ]
  9. Gilbert JM, Greenberg HB: Cleavage of rhesus rotavirus VP4 after arginine 247 is essential for rotavirus-like particle-induced fusion from without. J Virol. 1998 Jun;72(6):5323-7. doi: 10.1128/JVI.72.6.5323-5327.1998. [PubMed:9573313 ]
  10. Zarate S, Espinosa R, Romero P, Guerrero CA, Arias CF, Lopez S: Integrin alpha2beta1 mediates the cell attachment of the rotavirus neuraminidase-resistant variant nar3. Virology. 2000 Dec 5;278(1):50-4. doi: 10.1006/viro.2000.0660. [PubMed:11112480 ]
  11. Nejmeddine M, Trugnan G, Sapin C, Kohli E, Svensson L, Lopez S, Cohen J: Rotavirus spike protein VP4 is present at the plasma membrane and is associated with microtubules in infected cells. J Virol. 2000 Apr;74(7):3313-20. doi: 10.1128/jvi.74.7.3313-3320.2000. [PubMed:10708448 ]
  12. Zarate S, Cuadras MA, Espinosa R, Romero P, Juarez KO, Camacho-Nuez M, Arias CF, Lopez S: Interaction of rotaviruses with Hsc70 during cell entry is mediated by VP5. J Virol. 2003 Jul;77(13):7254-60. doi: 10.1128/jvi.77.13.7254-7260.2003. [PubMed:12805424 ]
  13. Lopez S, Arias CF: Multistep entry of rotavirus into cells: a Versaillesque dance. Trends Microbiol. 2004 Jun;12(6):271-8. doi: 10.1016/j.tim.2004.04.003. [PubMed:15165605 ]
  14. Kim IS, Trask SD, Babyonyshev M, Dormitzer PR, Harrison SC: Effect of mutations in VP5 hydrophobic loops on rotavirus cell entry. J Virol. 2010 Jun;84(12):6200-7. doi: 10.1128/JVI.02461-09. Epub 2010 Apr 7. [PubMed:20375171 ]
  15. Abdelhakim AH, Salgado EN, Fu X, Pasham M, Nicastro D, Kirchhausen T, Harrison SC: Structural correlates of rotavirus cell entry. PLoS Pathog. 2014 Sep 11;10(9):e1004355. doi: 10.1371/journal.ppat.1004355. eCollection 2014 Sep. [PubMed:25211455 ]
  16. Settembre EC, Chen JZ, Dormitzer PR, Grigorieff N, Harrison SC: Atomic model of an infectious rotavirus particle. EMBO J. 2011 Jan 19;30(2):408-16. doi: 10.1038/emboj.2010.322. Epub 2010 Dec 14. [PubMed:21157433 ]
  17. Liu Y, Xu S, Woodruff AL, Xia M, Tan M, Kennedy MA, Jiang X: Structural basis of glycan specificity of P[19] VP8*: Implications for rotavirus zoonosis and evolution. PLoS Pathog. 2017 Nov 14;13(11):e1006707. doi: 10.1371/journal.ppat.1006707. eCollection 2017 Nov. [PubMed:29136651 ]
  18. Trejo-Cerro O, Eichwald C, Schraner EM, Silva-Ayala D, Lopez S, Arias CF: Actin-Dependent Nonlytic Rotavirus Exit and Infectious Virus Morphogenetic Pathway in Nonpolarized Cells. J Virol. 2018 Feb 26;92(6). pii: JVI.02076-17. doi: 10.1128/JVI.02076-17. Print 2018 Mar 15. [PubMed:29263265 ]
  19. Dormitzer PR, Sun ZY, Wagner G, Harrison SC: The rhesus rotavirus VP4 sialic acid binding domain has a galectin fold with a novel carbohydrate binding site. EMBO J. 2002 Mar 1;21(5):885-97. doi: 10.1093/emboj/21.5.885. [PubMed:11867517 ]
  20. Yoder JD, Dormitzer PR: Alternative intermolecular contacts underlie the rotavirus VP5* two- to three-fold rearrangement. EMBO J. 2006 Apr 5;25(7):1559-68. doi: 10.1038/sj.emboj.7601034. Epub 2006 Mar 2. [PubMed:16511559 ]
  21. Kraschnefski MJ, Bugarcic A, Fleming FE, Yu X, von Itzstein M, Coulson BS, Blanchard H: Effects on sialic acid recognition of amino acid mutations in the carbohydrate-binding cleft of the rotavirus spike protein. Glycobiology. 2009 Mar;19(3):194-200. doi: 10.1093/glycob/cwn119. Epub 2008 Oct 30. [PubMed:18974199 ]
  22. Yu X, Dang VT, Fleming FE, von Itzstein M, Coulson BS, Blanchard H: Structural basis of rotavirus strain preference toward N-acetyl- or N-glycolylneuraminic acid-containing receptors. J Virol. 2012 Dec;86(24):13456-66. doi: 10.1128/JVI.06975-11. Epub 2012 Oct 3. [PubMed:23035213 ]