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Entry version 131 (23 Feb 2022)
Sequence version 3 (14 Apr 2009)
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Outer capsid protein VP4

Rotavirus A (strain RVA/Human/United States/Wa/1974/G1P1A[8]) (RV-A)
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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

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

VP8* Forms the head of the spikes and mediates the recognition of specific host cell surface glycans (PubMed:17306299).

It is the viral hemagglutinin and an important target of neutralizing antibodies (By similarity).

In sialic acid-dependent strains, VP8* binds to host cell sialic acid, most probably a ganglioside, providing the initial contact (PubMed:24501414).

In some other strains, VP8* mediates the attachment to histo-blood group antigens (HBGAs) for viral entry (By similarity).

UniRule annotation2 Publications


This strain probably does not use sialic acid to attach to the host cell.1 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

<p>The <a href="">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>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

Protein family/group databases

UniLectin database of carbohydrate-binding proteins


<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>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
<p>This subsection of the <a href="">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiRotavirus A (strain RVA/Human/United States/Wa/1974/G1P1A[8]) (RV-A)
<p>This subsection of the <a href="">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri10962 [NCBI]
<p>This subsection of the <a href="">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiVirusesRiboviriaOrthornaviraeDuplornaviricotaResentoviricetesReoviralesReoviridaeSedoreovirinaeRotavirusRotavirus A
<p>This subsection of the <a href="">Names and taxonomy</a> section only exists in viral entries and indicates the host(s) either as a specific organism or taxonomic group of organisms that are susceptible to be infected by a virus.<p><a href='/help/virus_host' target='_top'>More...</a></p>Virus hostiHomo sapiens (Human) [TaxID: 9606]
<p>This subsection of the <a href="">Names and taxonomy</a> section is present for entries that are part of a <a href="">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000006581 <p>A UniProt <a href="">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Genome

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

  • 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 associate 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

Keywords - Cellular componenti

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

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000410901 – 775Outer capsid protein VP4UniRule annotationAdd BLAST775
ChainiPRO_00000410911 – 230Outer capsid protein VP8*UniRule annotationAdd BLAST230
ChainiPRO_0000041092247 – 775Outer capsid protein VP5*UniRule annotationAdd BLAST529

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi317 ↔ 379UniRule annotation

<p>This subsection of the <a href="">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

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 inactive as long as the viral outer capsid is intact and would only be activated upon the solubilization of the latter.UniRule annotation


Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections ('Function', 'PTM / Processing', 'Pathology and Biotech') according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei230 – 231CleavageUniRule annotation2
Sitei240 – 241CleavageUniRule annotation2
Sitei246 – 247Cleavage; associated with enhancement of infectivityUniRule annotation2

Keywords - PTMi

Disulfide bond

Proteomic databases

PRoteomics IDEntifications database


<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

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.

Interacts with VP6.

Interacts with VP7.

UniRule annotation

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 (By similarity).

Interacts with host ITGA2 (via ITAG2 I-domain); this interaction occurs when ITGA2 is part of the integrin heterodimer ITGA2/ITGB1 (PubMed:16603530).

Interacts with host integrin heterodimer ITGA4/ITGB1 and ITGA4/ITGB7 (PubMed:16298987).

UniRule annotation2 Publications

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models


Database of comparative protein structure models


Protein Data Bank in Europe - Knowledge Base


Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence


<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi


Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni65 – 223Spike headUniRule annotationAdd BLAST159
Regioni247 – 479Antigen domainAdd BLAST233
Regioni247 – 478Spike body and stalk (antigen domain)UniRule annotationAdd BLAST232
Regioni307 – 309DGE motif; interaction with ITGA2/ITGB1 heterodimer1 Publication3
Regioni388 – 408Hydrophobic; possible role in virus entry into host cellUniRule annotationAdd BLAST21
Regioni509 – 775Spike footUniRule annotationAdd BLAST267

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and domains' section denotes the positions of regions of coiled coil within the protein.<p><a href='/help/coiled' target='_top'>More...</a></p>Coiled coili483 – 517UniRule annotationAdd BLAST35


Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi307 – 309DGE motif; interaction with ITGA2/ITGB1 heterodimerUniRule annotation3
Motifi447 – 449YGL motif; interaction with ITGA4UniRule annotation3
Motifi643 – 645KID motif; interaction with HSPA8UniRule annotation3

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

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

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the rotavirus VP4 family.UniRule annotation

Keywords - Domaini

Coiled coil

Family and domain databases

HAMAP database of protein families

MF_04132, Rota_A_VP4, 1 hit
MF_04125, Rota_VP4, 1 hit

Integrated resource of protein families, domains and functional sites

View protein in InterPro
IPR013320, ConA-like_dom_sf
IPR042546, Rota_A_VP4
IPR035330, Rota_VP4_MID
IPR038017, Rota_VP4_MID_sf
IPR035329, VP4_helical

Pfam protein domain database

View protein in Pfam
PF17477, Rota_VP4_MID, 1 hit
PF17478, VP4_helical, 1 hit

Superfamily database of structural and functional annotation

SSF111379, SSF111379, 1 hit
SSF49899, SSF49899, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="">length</a> and <a href="">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequencei

<p>This subsection of the <a href="">Sequence</a> section indicates if the <a href="">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="">Sequence</a> section indicates if the <a href="">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

P11193-1 [UniParc]FASTAAdd to basket
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Mass (Da):87,697
Last modified:April 14, 2009 - v3
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i1CE181B859F74FB0

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti64I → M in AAA66953 (PubMed:7530390).Curated1
Sequence conflicti100D → E (PubMed:3018754).Curated1
Sequence conflicti120T → L (PubMed:2839714).Curated1
Sequence conflicti265Q → E (PubMed:3018754).Curated1
Sequence conflicti331S → F in AAA66953 (PubMed:7530390).Curated1
Sequence conflicti388I → L in AAA47290 (PubMed:8389116).Curated1
Sequence conflicti525D → G in AAA47290 (PubMed:8389116).Curated1
Sequence conflicti618F → L (PubMed:2839714).Curated1
Sequence conflicti749N → K (PubMed:2839714).Curated1
Sequence conflicti759N → H (PubMed:2839714).Curated1
Sequence conflicti774K → R (PubMed:2839714).Curated1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database


GenBank nucleotide sequence database


DNA Data Bank of Japan; a nucleotide sequence database

Links Updated
M96825 Genomic RNA Translation: AAA47290.1
L34161 Genomic RNA Translation: AAA66953.1

Protein sequence database of the Protein Information Resource

A28839, VPXRW3

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
Links Updated
M96825 Genomic RNA Translation: AAA47290.1
L34161 Genomic RNA Translation: AAA66953.1
PIRiA28839, VPXRW3

3D structure databases

Select the link destinations:

Protein Data Bank Europe


Protein Data Bank RCSB


Protein Data Bank Japan

Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum

Protein family/group databases


Proteomic databases


Protocols and materials databases

ABCD curated depository of sequenced antibodies

P11193, 18 sequenced antibodies

Miscellaneous databases


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
IPR042546, Rota_A_VP4
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

MobiDB: a database of protein disorder and mobility annotations


<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiVP4_ROTHW
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P11193
Secondary accession number(s): Q05334, Q86202
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: April 14, 2009
Last modified: February 23, 2022
This is version 131 of the entry and version 3 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi



  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
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