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Protein

Outer capsid protein VP4

Gene
N/A
Organism
Rotavirus X (strain RVX/Human/China/NADRV-J19/1997/GXP[X]) (RV ADRV-N) (Rotavirus (isolate novel adult diarrhea rotavirus-J19))
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.Curated
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.Curated

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei245 – 246Probable cleavageCurated2
Sitei260 – 261Probable cleavageCurated2

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:
OrganismiRotavirus X (strain RVX/Human/China/NADRV-J19/1997/GXP[X]) (RV ADRV-N) (Rotavirus (isolate novel adult diarrhea rotavirus-J19))
Taxonomic identifieri335103 [NCBI]
Taxonomic lineageiVirusesdsRNA virusesReoviridaeSedoreovirinaeRotavirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000007663 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

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_00003698451 – 823Outer capsid protein VP4UniRule annotationAdd BLAST823
ChainiPRO_00003698461 – 245Outer capsid protein VP8*Add BLAST245
ChainiPRO_0000369847260 – 823Outer capsid protein VP5*Add BLAST564

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

Proteomic databases

PRIDEiQ45UF8

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.Curated

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi256 – 260Poly-Lys5

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

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
PfamiView protein in Pfam
PF17477 Rota_VP4_MID, 1 hit
SUPFAMiSSF111379 SSF111379, 1 hit

Sequencei

Sequence statusi: Complete.

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

Q45UF8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSLRSLLITT EAVGETTQTS DHQTSFSTRT YNEINDRPSL RIEKDGEKAY
60 70 80 90 100
CFKNLDPVRY DTRMGEYPFD YGGQSTENNQ LQFDLFTKDL KADTDIDLSD
110 120 130 140 150
DVKDDLKRQI MEYYQQGYRA IFLVRPQNQE QHYIASYSST NLNFTSQPSI
160 170 180 190 200
GVNLSILNKI QENKLYIYST QPHIPSVGCE MIAKIFRTDI DNENSLINYS
210 220 230 240 250
APVTVTISVT KATFGDTFVC NHPNMNYQDL IPTMTKNSIY HDVKRITKIH
260 270 280 290 300
EYINSKKKKK NSTSKIGGIQ IAESKDGFWK ILTKNYQIKL KFGVEGYGVM
310 320 330 340 350
GGTFGNWLID SGFKTVETNY EYQRNGKTIN ATTVASVKPS RKCGTRSPVF
360 370 380 390 400
GQLQFSGEMM VLSHNDILTV FYTEREWALS NAIYAKNFAT DFKRQFEITA
410 420 430 440 450
QSDELLVRTN VVPHTIKNTP GKALMEYSHG GFGQIDTSDY TGMALTFRFR
460 470 480 490 500
CISEDLPEGY YDRDKALAFA NVGLTSFQDR QEANGTYWVY NTSTVGFGSC
510 520 530 540 550
YPKKEFEYDI NVTYTTLLPS DPEFTTGGTN YAQSVTAVLE ESFINLQNQV
560 570 580 590 600
NEMLTRMNIS DLTSGVMSVF SVATSFPQIL DGISDLLKAA SSAFKKVKGK
610 620 630 640 650
VGSVAKRLRG KRYVRLFDEN VSIEETPRFL DSIRSSRRPS ILSNMFNDDE
660 670 680 690 700
TFTALHTLAS RTNSVASDVT YLQPIITTRI ANSTPPVIAP ASSVTYAKLK
710 720 730 740 750
DISKIINAEI DPKSIMEFNQ ISNTISILDS TKKLAQYAVD PDIIDGILNK
760 770 780 790 800
MVGGHARSLF SLKVRKHLLD AVEKDAFVKY NYHDLMGKLL NDRELLDITN
810 820
NLSSQKQFEL AKEFRDLLIN ALA
Length:823
Mass (Da):92,912
Last modified:September 13, 2005 - v1
Checksum:iFD0AA4BA99AEB512
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ113899 Genomic RNA Translation: AAZ03487.1
RefSeqiYP_392492.1, NC_007550.1

Genome annotation databases

GeneIDi5076652
KEGGivg:5076652

Similar proteinsi

Entry informationi

Entry nameiVP4_ROTJ1
AccessioniPrimary (citable) accession number: Q45UF8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 14, 2009
Last sequence update: September 13, 2005
Last modified: June 20, 2018
This is version 50 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, Reference proteome

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