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UniProtKB - A2T3T2 (VP4_ROTSH)

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Protein

Outer capsid protein VP4

Gene
N/A
Organism
Rotavirus A (isolate RVA/Monkey/South Africa/SA11-H96/1958/G3P5B[2]) (RV-A) (Simian Agent 11 (isolate SI/South Africa/H96/58))
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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 (PubMed:1649333). 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:9144247, 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 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. 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 (By similarity).1 PublicationUniRule annotation2 Publications
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 by exposing VP5* hydrophobic region. In integrin-dependent strains, VP5* targets the integrin heterodimer ITGA2/ITGB1 for cell attachment.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. 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.UniRule annotation

Miscellaneous

In group A rotaviruses, VP4 defines the P serotype.UniRule annotation
Some rotavirus strains are neuraminidase-sensitive and require sialic acid to attach to the cell surface. Some rotavirus strains are integrin-dependent. Some rotavirus strains depend on ganglioside for their entry into the host cell. Hsp70 also seems to be involved in the entry of some strains.UniRule annotation1 Publication
This strain probably uses sialic acid to attach to the host cell.1 PublicationUniRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei101Binding to sialic acidUniRule annotation1
Sitei190Binding to sialic acidUniRule annotation1

GO - Biological processi

View the complete GO annotation on QuickGO ...

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 A (isolate RVA/Monkey/South Africa/SA11-H96/1958/G3P5B[2]) (RV-A) (Simian Agent 11 (isolate SI/South Africa/H96/58))
Taxonomic identifieri450149 [NCBI]
Taxonomic lineageiViruses › dsRNA viruses › Reoviridae › Sedoreovirinae › Rotavirus › Rotavirus A ›
Virus hostiChlorocebus pygerythrus (Vervet monkey) (Cercopithecus pygerythrus) [TaxID: 60710]
Proteomesi
  • UP000001119 Componenti: Genome

Subcellular locationi

Outer capsid protein VP4 :
  • Virion UniRule annotation1 Publication
  • Host rough endoplasmic reticulum UniRule annotation
  • Host cell membrane UniRule annotation
  • host cytoskeleton UniRule annotation
  • Host endoplasmic reticulum-Golgi intermediate compartment UniRule annotation
    • Note: The outer layer contains 180 copies of VP4, grouped as 60 dimers (PubMed:2153941). 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. VP4 also seems to associates with lipid rafts of the host cell membrane probably for the exit of the virus from the infected cell by an alternate pathway (By similarity).UniRule annotation1 Publication
Outer capsid protein VP8* :
  • Virion UniRule annotation1 Publication
    • Note: Outer capsid protein.UniRule annotation
Outer capsid protein VP5* :
  • Virion UniRule annotation1 Publication
    • Note: Outer capsid protein.UniRule annotation

GO - Cellular componenti

View the complete GO annotation on QuickGO ...

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003681161 – 776Outer capsid protein VP4UniRule annotationAdd BLAST776
ChainiPRO_00003681171 – 231Outer capsid protein VP8*UniRule annotationAdd BLAST231
ChainiPRO_0000368118248 – 776Outer capsid protein VP5*UniRule annotationAdd BLAST529

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi203 ↔ 216UniRule annotation
Disulfide bondi318 ↔ 380UniRule annotation

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
Sitei241 – 242CleavageUniRule annotation2
Sitei247 – 248Cleavage; associated with enhancement of infectivityUniRule annotation2

Keywords - PTMi

Disulfide bond

Interactioni

Subunit structurei

Outer capsid protein VP4: Homotrimer. Outer capsid protein VP4: 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 (By similarity). Outer capsid protein VP4: Interacts with VP6 (By similarity). Outer capsid protein VP4: Interacts with VP7 (By similarity). 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. The two- to three-fold reorganization and fold-back of VP5* may be linked to membrane penetration, by exposing its hydrophobic region (By similarity). Outer capsid protein VP5*: Interacts with host ITGA2 (via ITAG2 I-domain); this interaction occurs when ITGA2 is part of the integrin heterodimer ITGA2/ITGB1 (PubMed:9144247).UniRule annotation1 Publication

Structurei

3D structure databases

ProteinModelPortaliA2T3T2
SMRiA2T3T2
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni51 – 78Disorded; interaction with the intermediate capsid protein VP6UniRule annotationAdd BLAST28
Regioni65 – 224Spike headUniRule annotationAdd BLAST160
Regioni248 – 479Spike body and stalk (antigen domain)UniRule annotationAdd BLAST232
Regioni308 – 310DGE motif; interaction with ITGA2/ITGB1 heterodimer1 Publication3
Regioni312 – 326DisordedUniRule annotationAdd BLAST15
Regioni389 – 409Hydrophobic; possible role in virus entry into host cellUniRule annotationAdd BLAST21
Regioni510 – 776Spike footUniRule annotationAdd BLAST267

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili484 – 511UniRule annotationAdd BLAST28

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi308 – 310DGE motif; interaction with ITGA2/ITGB1 heterodimerUniRule annotation3
Motifi448 – 450YGL motif; interaction with ITGA4UniRule annotation3
Motifi644 – 646KID motif; interaction with HSPA8UniRule annotation3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi560 – 616Ser-richAdd BLAST57

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

KOiK19249
OrthoDBiVOG0900002L

Family and domain databases

HAMAPiMF_04132 Rota_A_VP4, 1 hit
MF_04125 Rota_VP4, 1 hit
InterProiView protein in InterPro
IPR013320 ConA-like_dom_sf
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
SSF49899 SSF49899, 1 hit

Sequencei

Sequence statusi: Complete.

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

A2T3T2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASLIYRQLL TNSYTVDLSD EIQEIGSTKS QNVTINPGPF AQTGYAPVNW 
        60         70         80         90        100
GPGEINDSTT VEPLLDGPYQ PTTFNPPVDY WMLLAPTTPG VIVEGTNNTD 
       110        120        130        140        150
RWLATILIEP NVQSENRTYT IFGIQEQLTV SNTSQDQWKF IDVVKTTANG 
       160        170        180        190        200
SIGQYGPLLS SPKLYAVMKH NEKLYTYEGQ TPNARTAHYS TTNYDSVNMT 
       210        220        230        240        250
AFCDFYIIPR SEESKCTEYI NNGLPPIQNT RNVVPLSLTA RDVIHYRAQA 
       260        270        280        290        300
NEDIVISKTS LWKEMQYNRD ITIRFKFANT IIKSGGLGYK WSEISFKPAN 
       310        320        330        340        350
YQYTYTRDGE EVTAHTTCSV NGVNDFSFNG GYLPTDFVVS KFEVIKENSY 
       360        370        380        390        400
VYIDYWDDSQ AFRNVVYVRS LAANLNSVMC TGGSYNFSLP VGQWPVLTGG 
       410        420        430        440        450
AVSLHSAGVT LSTQFTDFVS LNSLRFRFRL AVEEPHFKLT RTRLDRLYGL 
       460        470        480        490        500
PAADPNNGKE YYEIAGRFSL ISLVPSNDDY QTPIANSVTV RQDLERQLGE 
       510        520        530        540        550
LREEFNALSQ EIAMSQLIDL ALLPLDMFSM FSGIKSTIDA AKSMATNVMK 
       560        570        580        590        600
KFKKSGLANS VSTLTDSLSD AASSISRGSS IRSIGSSASA WTDVSTQITD 
       610        620        630        640        650
ISSSVSSVST QTSTISRRLR LKEMATQTEG MNFDDISAAV LKTKIDKSTQ 
       660        670        680        690        700
ISPNTIPDIV TEASEKFIPN RAYRVINNDD VFEAGIDGKF FAYKVDTFEE 
       710        720        730        740        750
IPFDVQKFAD LVTDSPVISA IIDFKTLKNL NDNYGITKQQ AFNLLRSDPR 
       760        770 
VLREFINQDN PIIRNRIEQL IMQCRL
Length:776
Mass (Da):86,775
Last modified:March 6, 2007 - v1
Checksum:iEA9B43CE96CC53CF
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ841262 Genomic RNA Translation: ABH10616.1
RefSeqiYP_002302230.1, NC_011510.2

Genome annotation databases

GeneIDi7011406
KEGGivg:7011406

Similar proteinsi

Entry informationi

Entry nameiVP4_ROTSH
AccessioniPrimary (citable) accession number: A2T3T2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 14, 2009
Last sequence update: March 6, 2007
Last modified: June 20, 2018
This is version 65 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

Documents

  1. SIMILARITY comments
    Index of protein domains and families

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