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Protein

Outer capsid protein VP4

Gene
N/A
Organism
Rotavirus C (strain RVC/Pig/United States/Cowden/1980) (RV-C)
Status
Reviewed-Annotation score: -Protein inferred from homologyi

Functioni

Outer capsid protein VP4: 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 Ca2+ 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.UniRule annotation
Outer capsid protein VP5*: 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.UniRule annotation
Outer capsid protein VP8*: 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.UniRule annotation

GO - Biological processi

Keywordsi

Molecular functionHemagglutinin
Biological processHost-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 VP4UniRule annotation
Alternative name(s):
HemagglutininUniRule annotation
Cleaved into the following 2 chains:
Outer capsid protein VP8*UniRule annotation
Outer capsid protein VP5*UniRule annotation
OrganismiRotavirus C (strain RVC/Pig/United States/Cowden/1980) (RV-C)
Taxonomic identifieri10916 [NCBI]
Taxonomic lineageiVirusesdsRNA virusesReoviridaeSedoreovirinaeRotavirus
Virus hostiSus scrofa (Pig) [TaxID: 9823]
Proteomesi
  • UP000008175 Componenti: Genome

Subcellular locationi

Outer capsid protein VP4 :
  • Virion UniRule annotation
  • Host rough endoplasmic reticulum UniRule annotation
  • Host cell membrane UniRule annotation
  • Host endoplasmic reticulum-Golgi intermediate compartment UniRule annotation
  • Note: The outer layer contains 180 copies of VP4, grouped as 60 dimers. 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.UniRule annotation
Outer capsid protein VP8* :
  • Virion UniRule annotation
  • Note: Outer capsid protein.UniRule annotation
Outer capsid protein VP5* :
  • Virion UniRule annotation
  • Note: Outer capsid protein.UniRule annotation

GO - Cellular componenti

Keywords - Cellular componenti

Capsid protein, Host cell membrane, Host endoplasmic reticulum, Host membrane, Membrane, Outer capsid protein, Virion

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000410991 – 736Outer capsid protein VP4UniRule annotationAdd BLAST736
ChainiPRO_00000411001 – 231Outer capsid protein VP8*UniRule annotationAdd BLAST231
ChainiPRO_0000041101248 – 736Outer capsid protein VP5*UniRule annotationAdd BLAST489

Post-translational modificationi

Outer capsid protein VP4: 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. Cleavage of VP4 by trypsin probably occurs in vivo in the lumen of the intestine prior to infection of enterocytes. Trypsin seems to be incorporated into the three-layered viral particles but remains inctive as long as the viral outer capsid is intact and would only be activated upon the solubilization of the latter.UniRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei231 – 232CleavageUniRule annotation2
Sitei247 – 248CleavageUniRule annotation2

Interactioni

Subunit structurei

Outer capsid protein VP4: Homotrimer. 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. Outer capsid protein VP4: Interacts with VP6. Outer capsid protein VP4: Interacts with VP7. Outer capsid protein VP5*: Homotrimer. 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.UniRule annotation

Structurei

3D structure databases

ProteinModelPortaliP26193
SMRiP26193
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili495 – 515UniRule annotationAdd BLAST21

Domaini

Outer capsid protein VP4: The VP4 spike is divided into a foot, a stalk and body, and a head.UniRule annotation

Sequence similaritiesi

Belongs to the rotavirus VP4 family.UniRule annotation

Keywords - Domaini

Coiled coil

Phylogenomic databases

OrthoDBiVOG0900002L

Family and domain databases

HAMAPiMF_04125 Rota_VP4, 1 hit
InterProiView protein in InterPro
IPR035330 Rota_VP4_MID
IPR038017 Rota_VP4_MID_sf
IPR000416 VP4_concanavalin-like
IPR035329 VP4_helical
PfamiView protein in Pfam
PF17477 Rota_VP4_MID, 1 hit
PF00426 VP4_haemagglut, 1 hit
PF17478 VP4_helical, 1 hit
SUPFAMiSSF111379 SSF111379, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P26193-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASSLYQQLI SQNYYSIGNE ILTDQQTTET VVDYVDAGNY TYAQLPPTKW
60 70 80 90 100
GARGTFKSAF NVSNITGPHT NTIIEWSNLL NSNGWVIYQK PANTTKLFKH
110 120 130 140 150
GPETYNSNLA AFELWYGKAG TSVTSDYYSS LQNNEKTVTA TSDSLILFWN
160 170 180 190 200
EGSTVLANKK VNFSWDMGGM LIKPTRGNRV DICMANMNDF NSSIFNWEEW
210 220 230 240 250
KHEFPRSDVN INVNMYTDYY LASEDPYTEL KALQQPNITT FEMKMMKIIR
260 270 280 290 300
NGSINLNEVV SKDSLWQEVR YARDITLECK IESEVVKGGG WGYDYTSVAF
310 320 330 340 350
KTVNHTYTYT RAGEIVNAHV TISFNNMKER SYGGSLPTDF KIGRFDVIDT
360 370 380 390 400
DTYMYIDYWD DSEIFKNMVY VRDLSANIGG FFYYAEMSYY FQIPVGAHPG
410 420 430 440 450
LHSSGVRFVY ERCLLSQQFT DQVALNSMRF IFRVTESNGW FMTSGNINTR
460 470 480 490 500
RIASGTGFAY ADGHTSQTVG NITFISLIPS NPNYQTPIAS SSTVRMDLER
510 520 530 540 550
KINDLRNDFN QLANSVALGD ILSLATSPLT FANLLESVPA IASSVKDVAA
560 570 580 590 600
NVMKKFRNTK MFKKATKAKY SEFIIGDLLE DVTNVARNSN GMNFDDITSA
610 620 630 640 650
VMVSTTNKLQ LTDVDTLSEI VARSADNFIP NRSYRMIEDG IVYEATPKRT
660 670 680 690 700
FSYDLTTLQQ REFDIDKFMR LASKSPVISA IVDFATLKAM RETYGVGTDV
710 720 730
IYKLVASDAP TILSFIDNNN PLIKSRIEEL LRQCRL
Length:736
Mass (Da):83,232
Last modified:May 1, 1992 - v1
Checksum:i356F9226D5016577
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M74218 Genomic DNA Translation: AAB00802.1
PIRiD40822 VPXRPC

Similar proteinsi

Entry informationi

Entry nameiVP4_ROTPC
AccessioniPrimary (citable) accession number: P26193
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: May 1, 1992
Last modified: June 20, 2018
This is version 90 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome

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