A0A4Y6I3M0 · A0A4Y6I3M0_9REOV

  • Protein
    Non-structural glycoprotein 4
  • Status
    UniProtKB unreviewed (TrEMBL)
  • Organism
  • Amino acids
  • Protein existence
    Evidence at transcript level
  • Annotation score
    3/5

Function

function

Plays an essential role in the virus replication cycle by acting as a viroporin. Creates a pore in the host reticulum endoplasmic and as a consequence releases Ca2+ in the cytoplasm of infected cell. In turn, high levels of cytoplasmic calcium trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication and immature particle assembly.
The secreted form acts as an enterotoxin that causes phospholipase C-dependent elevation of the intracellular calcium concentration in host intestinal mucosa cells. Increased concentration of intracellular calcium disrupts the cytoskeleton and the tight junctions, raising the paracellular permeability. Potentiates chloride ion secretion through a calcium ion-dependent signaling pathway, inducing age-dependent diarrhea. To perform this enterotoxigenic role in vivo, NSP4 is released from infected enterocytes in a soluble form capable of diffusing within the intestinal lumen and interacting with host plasma membrane receptors on neighboring epithelial cells such as integrins ITGA1/ITGB1 and ITGA2/ITGB1.

Features

Showing features for binding site.

117520406080100120140160
TypeIDPosition(s)Description
Binding site120Ca2+ (UniProtKB | ChEBI)
Binding site123Ca2+ (UniProtKB | ChEBI)

GO annotations

all annotationsall molecular functionvirus receptor activitydna bindingrna bindingcytoskeletal motor activitycatalytic activitygtpase activitystructural molecule activitytransporter activitycytoskeletal protein bindinglipid bindingcyclase activityantioxidant activityoxidoreductase activitytransferase activityhydrolase activitylyase activityisomerase activityligase activityprotein tag activitycargo receptor activityhistone bindingprotein folding chaperonetranslation regulator activitynutrient reservoir activityreceptor ligand activitymolecular transducer activitymolecular adaptor activitytoxin activitycell adhesion mediator activitymolecular function regulator activityvirus coreceptor activitycatalytic activity, acting on a proteincatalytic activity, acting on dnacatalytic activity, acting on rnamolecular carrier activitytranscription regulator activitygeneral transcription initiation factor activitymolecular sensor activitymolecular sequestering activityatp-dependent activityother molecular functionall biological processmitotic cell cyclecytokinesiscytoplasmic translationimmune system processmuscle system processcirculatory system processrenal system processrespiratory system processcarbohydrate metabolic processgeneration of precursor metabolites and energydna replicationdna repairdna recombinationchromatin organizationdna-templated transcriptionregulation of dna-templated transcriptiontrna metabolic processprotein foldingprotein glycosylationamino acid metabolic processmodified amino acid metabolic processlipid metabolic processvitamin metabolic processsulfur compound metabolic processintracellular protein transportnucleocytoplasmic transportautophagyinflammatory responsemitochondrion organizationcytoskeleton organizationmicrotubule-based movementperoxisome organizationlysosome organizationchromosome segregationcell adhesionestablishment or maintenance of cell polarityprogrammed cell deathphotosynthesismrna metabolic processsnrna metabolic processvesicle-mediated transportreproductive processdigestive system processsignalingcell differentiationprotein catabolic processextracellular matrix organizationregulatory ncrna-mediated gene silencingtelomere organizationcell junction organizationwound healingribosome biogenesiscilium organizationanatomical structure developmentcell motilitynervous system processendocrine processprotein maturationtransmembrane transportnucleobase-containing small molecule metabolic processhepaticobiliary system processmembrane organizationprotein-containing complex assemblycell wall organization or biogenesisnitrogen cycle metabolic processprotein localization to plasma membranedefense response to other organismdetoxificationmeiotic nuclear divisionmitotic nuclear divisionmitochondrial gene expressioncarbohydrate derivative metabolic processother biological processall cellular componentnuclear chromosomeextracellular regionextracellular spacecell wallnucleusnuclear envelopenucleoplasmchromosomenucleolusmitochondrionlysosomeendosomevacuoleperoxisomeendoplasmic reticulumgolgi apparatuslipid dropletmicrotubule organizing centercytosolribosomecytoskeletonplasma membraneciliumplastidthylakoidexternal encapsulating structureextracellular matrixcytoplasmic vesicleorganelleother cellular component
Cell color indicative of number of GO terms
AspectTerm
Cellular Componentextracellular region
Cellular Componenthost caveola
Cellular Componenthost cell rough endoplasmic reticulum membrane
Cellular Componentmembrane
Molecular Functionchannel activity
Molecular Functionmetal ion binding
Molecular Functiontoxin activity
Biological Processinduction by virus of host autophagy
Biological Processmonoatomic ion transmembrane transport

Keywords

Names & Taxonomy

Protein names

  • Recommended name
    Non-structural glycoprotein 4
  • Short names
    NSP4
  • Alternative names
    • NCVP5
    • NS28

Organism names

  • Taxonomic identifier
  • Organism
    Rotavirus A
  • Strain
    • RVA/Pig-wt/BGD/H14020027/G4P[49]
  • Taxonomic lineage
    Viruses > Riboviria > Orthornavirae > Duplornaviricota > Resentoviricetes > Reovirales > Sedoreoviridae > Rotavirus

Accessions

  • Primary accession
    A0A4Y6I3M0

Subcellular Location

Host rough endoplasmic reticulum membrane
; Single-pass type III membrane protein
Host membrane, host caveola
; Single-pass type III membrane protein
Secreted
Note: NSP4 localizes also in vesicular structures which contain autophagosomal markers and associate with viroplasms in virus-infected cells. Additionally, a soluble form of glycosylated NSP4 is secreted despite retention of its transmembrane domain.

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-28Lumenal
Transmembrane29-46Helical
Topological domain52-175Cytoplasmic

Keywords

PTM/Processing

Features

Showing features for glycosylation.

TypeIDPosition(s)Description
Glycosylation8N-linked (GlcNAc...) asparagine; by host
Glycosylation18N-linked (GlcNAc...) asparagine; by host

Post-translational modification

The N-glycosyl content is primarily Man9GlcNAc, with a small amount of Man8GlcNAc.

Keywords

Interaction

Subunit

Homotetramer. Interacts with the immature particle in the viroplasm. Interacts with host CAV1, early and late in infection. Interacts with host integrin ITGA1/ITGB1 heterodimer. Interacts with host integrin ITGA2/ITGB1 heterodimer. Interaction with microtubules blocks trafficking to the Golgi apparatus.

Family & Domains

Domain

Binds 1 calcium ion per tetramer.

Sequence similarities

Belongs to the rotavirus NSP4 family.

Keywords

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    175
  • Mass (Da)
    20,248
  • Last updated
    2019-09-18 v1
  • Checksum
    AFC7FEA45ADD92FC
MDKLADLNYTLSVITLMNDTLHSIIQDPGMAYFPYIASVLTVLFTLHKASIPTMKIALRTSKCSYKVIKYCMVTIINTLLKLAGYKGQVTTKDEIEQQMDRIVKEMRRQLEMIDKLTTREIEQVELLKRIHDKLSIRPVDAIDMSKEFNQKNIRTLDEWENGKNPYEPSEVTASM

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
MK227396
EMBL· GenBank· DDBJ
QDF63668.1
EMBL· GenBank· DDBJ
mRNA

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Disclaimer

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