Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Outer capsid protein VP4

Gene
N/A
Organism
Rotavirus A (strain RVA/Human/Japan/K8/1977/G1P3A[9]) (RV-A)
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. 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. 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.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 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

This strain probably does not use sialic acid to attach to the host cell.1 Publication1 Publication
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 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 A (strain RVA/Human/Japan/K8/1977/G1P3A[9]) (RV-A)
Taxonomic identifieri39012 [NCBI]
Taxonomic lineageiVirusesdsRNA virusesReoviridaeSedoreovirinaeRotavirusRotavirus A
Virus hostiHomo sapiens (Human) [TaxID: 9606]

Subcellular locationi

Outer capsid protein VP4 :
  • Virion UniRule annotation
  • 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. 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.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 cytoplasm, Host cytoskeleton, Host endoplasmic reticulum, Host membrane, Membrane, Outer capsid protein, Virion

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000410571 – 775Outer capsid protein VP4UniRule annotationAdd BLAST775
ChainiPRO_00000410581 – 231Outer capsid protein VP8*UniRule annotationAdd BLAST231
ChainiPRO_0000041059248 – 775Outer capsid protein VP5*UniRule annotationAdd BLAST528

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
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

Proteomic databases

PRIDEiQ01641

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

Secondary structure

1775
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi66 – 69Combined sources4
Beta strandi71 – 75Combined sources5
Beta strandi80 – 85Combined sources6
Beta strandi87 – 96Combined sources10
Beta strandi98 – 100Combined sources3
Beta strandi102 – 108Combined sources7
Beta strandi110 – 121Combined sources12
Beta strandi124 – 132Combined sources9
Beta strandi138 – 147Combined sources10
Beta strandi153 – 160Combined sources8
Beta strandi165 – 170Combined sources6
Beta strandi173 – 180Combined sources8
Beta strandi185 – 191Combined sources7
Beta strandi198 – 209Combined sources12
Helixi210 – 212Combined sources3
Helixi213 – 222Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5CAZX-ray1.80A64-224[»]
5CB7X-ray1.35A/B64-224[»]
ProteinModelPortaliQ01641
SMRiQ01641
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
Regioni312 – 326DisordedUniRule annotationAdd BLAST15
Regioni389 – 409Hydrophobic; possible role in virus entry into host cellUniRule annotationAdd BLAST21
Regioni510 – 775Spike footUniRule annotationAdd BLAST266

Coiled coil

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

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi448 – 450YGL motif; interaction with ITGA4UniRule annotation3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi560 – 615Ser-richAdd BLAST56

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

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
IPR035329 VP4_helical
PfamiView protein in Pfam
PF17477 Rota_VP4_MID, 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.

Q01641-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASLIYRQLL SNSYVTNISD EVNEIGTKKT TNVTVNPGPF AQTGYAPVDW
60 70 80 90 100
GHGELPDSTL VQPTLDGPYQ PTSLNLPVDY WMLIAPTREG KVAEGTNTTD
110 120 130 140 150
RWFACVLVEP NVQNTQRQYV LDGQNVQLHV SNDSSTSWKF ILFIKLTPYG
160 170 180 190 200
TYTQYSTLST PHKLCAWMKR DNRVYWYQGA TPNASESYYL TINNDNSNVS
210 220 230 240 250
SDAEFYLIPQ SQTAMCTQYI NNGLPPIQNT RNIVPVNITS RQIKDVRAQM
260 270 280 290 300
NEDIVISKTS LWKEMQYNRD IIIRFKFANS IIKSGGLGYK WSEISFKPMN
310 320 330 340 350
YQYTYTRDEE EVTAHTTCSV NGVNDFNYNG GTLPTDFAIS RFEVIKENSY
360 370 380 390 400
VYVDYWDDSQ AFRNMVYVRS LAANLNDVVC SGGSYSFALP VGNHPVMSGG
410 420 430 440 450
AVTLTSAGVT LSTQYTDYVS LNSLQFRFRL AVSEPSFSIS RTRMSGIYGL
460 470 480 490 500
PAVNPNNSAE YYEIAGRFSL ISLVPTNDDY QTPIANSVTV RQDLERQLGE
510 520 530 540 550
LREEFNSLSQ EIAVSQLIDL ATLPLDMFSM FSGIKSTVEA VKSMTTNVMK
560 570 580 590 600
RFKTSSLANA ISDLTSNMSE AASSVRLTSV RSVGTITLPR ARVSLQVGDD
610 620 630 640 650
LRSMQDVSTQ VSNVSRNLRL KEFTTQTDTL SFDDISAAVL KTKLDKSTQI
660 670 680 690 700
SQQTMPDIIA ESSEKFIPKR SYRIVDEDIR FETGIDGTFY AYKVDTFNEI
710 720 730 740 750
PFDMERFNKL ITDSPVLSAI IDFKTLKNLN DNYGITKKQA MELLHSNPKT
760 770
LKEFINNNNP IIRNRIENLI SQCRL
Length:775
Mass (Da):87,250
Last modified:April 1, 1993 - v1
Checksum:i43F8CC155785D5AB
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D90260 Genomic RNA Translation: BAA14307.1

Similar proteinsi

Entry informationi

Entry nameiVP4_ROTHJ
AccessioniPrimary (citable) accession number: Q01641
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: May 23, 2018
This is version 94 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

3D-structure

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health